Paul Giamatti is an actor who becomes so impassioned with the characters and roles that he plays that he has trouble disassociating himself from the character after the scene is done. As a result, his mind and spirit are a tangled mass of emotions that he seems to have trouble separating from his own feelings. As he struggles to play Uncle Vanya, he reads an article in The New Yorker regarding "Soul Storage," a procedural clinic that physically removes one's soul from his body. While hesitant at first to go through with such a procedure, being unsure how it would affect him, Paul decides to go ahead. On visiting the clinic he discovers that most souls come out as gray matter or clouds. He decides to go ahead, declining the offer to look at his soul as it happens. He is distressed to discover that his soul comes out looking just like a chickpea. He has it stored in the clinic and returns to his life with 5% of his soul remaining. He is told this is like residue, enough to leave him with some emotional reaction, like affection for his loved ones and hobbies but not very deep or complex feeling to new things. He at first feels more relaxed, however his life begins to fall apart; he has trouble associating with or making love to his wife Claire despite wanting to. Lacking in emotional intelligence in new situations, he is easily bored and says insensitive things, such as telling a friend to just "pull the plug" on her comatose mother, and his acting for the Chekhov play lacks believability. Not wanting his soul back just yet, he instead obtains the soul of what he is told is a Russian poet, whose memories entice him to be curious about her and her life as well as obtain a curiosity of his own. This Russian soul allows him to play Uncle Vanya excellently, but the experience overwhelms him and he decides to get his own soul back. Paul's world is turned upside down when Nina, a Russian soul mule who transports people's souls to and from Russia, steals Paul's soul for the wife of her boss at the Russian soul-storage operation, who aspires to be an actress. She receives Paul's soul, believing it to be the soul of Al Pacino. Her acting and happiness improve. Nina, the mule who carried Paul's soul and has become curious about him, eventually reveals the whereabouts of his soul, helping him to get it back. As the pair investigate the soul of Olga the poet, which he had 'rented' during this period, they learn that she committed suicide after not being able to get it back after selling it. Paul and Nina get his soul back, and after looking into it through the use of special goggles to reassociate himself to it, he returns to New York a happier man. Nina's soul is found, but Paul is told that it is unrecoverable due to the residues of souls that she has carried.

When two grade-school boys get into a fight in the park that results in one boy, Zachary Cowan, hitting the other, Ethan Longstreet, in the face with a stick, their parents meet in a Brooklyn apartment to discuss the matter. Zachary's parents, Alan (Christoph Waltz) and Nancy Cowan (Kate Winslet), visit the home of Michael (John C. Reilly) and Penelope Longstreet (Jodie Foster), Ethan's parents. Their meeting is initially intended to be short, but due to various circumstances, the conversation continues to draw out.In fact, Alan and Nancy begin to leave the apartment on two occasions, but are drawn back in to further discussion. At first, the couples are friendly to each other, but their respective comments start to hurt feelings, making everyone argue with one another. Apart from fighting amongst themselves, the couples blame each other about who is responsible for the fight between their sons. Nancy calls the Longstreets "superficially fair-minded" and Penelope and Michael complain about Alan's arrogant and dull attitude. Everyone also gets irritated with Alan when he accepts endless business phone calls on his BlackBerry, interrupting the discussion, and showing he has more interest in his business problems than the matter at hand. Michael also receives many phone calls from his ailing mother, to his frustration. Nancy accuses Michael of being a murderer because he, annoyed by the constant noise it made during the night, had earlier turned his daughter Courtney's pet hamster loose in the street. Penelope becomes emotional about the hamster and with everyone arguing with each other. Other issues include a risky drug Alan is working to defend and Michael's mother has been prescribed, and the question of idealism and responsibility that is part of Penelope's current work. Michael offers everyone a glass of fine Scotch. Penelope claims she doesn't "get drunk" and Nancy drinks way too many and finally stops Alan's phone calls by dropping his cellphone in Penelope's flower vase full of tulips and water. Penelope and Nancy both laugh uproariously while Michael and Alan try to blow-dry the BlackBerry. The conversation continues to decay into personal attacks and opinionated statements and, eventually, epithets are uttered. Penelope is ranting, calling Nancy's son a "snitch", and Nancy's true colors are revealed when she destroys the tulips and drunkenly and vulgarly states she is glad that her son beat up Penelope's and Michael's son. The couples realize the conversation is going nowhere. Alan's BlackBerry, lying on the coffee table, vibrates, and all four stare at it. The film cuts to the hamster, alive and well in the park, where Ethan and Zachary are reconciling on their own.

Amy Benic takes a vacation at a spa outside New York City. Virgil Adamson is a masseur at the spa and gives Amy a massage. Amy inexplicably cries and Virgil comforts her. While complimenting Virgil on the massage, Amy realizes that Virgil is blind. Virgil asks her out, and the two eventually begin a relationship. Virgil lives alone, though his over-protective sister Jennie lives next door and takes care of him. Virgil reveals that he went blind when he was three and that the last thing he saw was something fluffy. While researching Virgil's condition, Amy learns of Doctor Charles Aaron, a specialist in eye treatment who suggests to Virgil that, with surgery, he could restore his sight. Virgil angrily refuses. Jennie reveals that their father left the family after putting Virgil through several kinds of treatments in order to restore his sight. Virgil eventually decides he will give the operation a try. It is a success, but after Virgil regains sight, he becomes confused and disoriented, unable to perceive light and distance. Dr. Aaron suggests that he should visit Phil Webster, a visual physiotherapist. Webster in turn suggests that Virgil needs to learn everything from scratch himself, through experience. Virgil and Amy begin living in New York City. The pair begin drifting apart, as Virgil finds it hard to decipher the look on Amy's face at times. Amy finds herself constantly having to explain basic things to Virgil. While at a party, Virgil walks into a glass pane due to his poor perception. Virgil's father sees him on television and arranges a reunion; Virgil goes to his father's workplace, but decides at the last minute that he cannot face him yet. On one of the regular visits with Webster, they engage in a deep conversation, where Webster notes that instead of just "seeing", Virgil should "look"; there are a lot of things that sight alone cannot solve. Virgil confesses that he and Amy are drifting apart, but insists that Amy is the most important thing in his life. Upon returning from a work trip to Atlanta, where she and her ex-husband shared a sensual moment, Amy decides to save the relationship. She finds Virgil in a park looking for "the horizon" in the city. Virgil's sight begins deteriorating. After consulting with Dr. Aaron, Virgil realizes that he is losing his sight yet again. He decides to look for his father. Virgil reveals to him that he is going blind again, and asks him why he left. His father tells him that he felt he was a failure when he did not find a way to help his son regain sight. Virgil states that he should not have left because his mother and sister suffered greatly after his father walked away. Virgil looks for Amy, who tells him about her plans to travel with him to places like Egypt and Europe. Withholding the fact that he is again going blind, Virgil tells her there is one thing he really wants to see, and brings her to a New York Rangers game. At the game, Virgil realizes that the "fluffy cloud" he last remembers seeing was cotton candy. He suffers a lengthened vision blackout and admits to Amy that he is going blind, which Amy refuses to accept. Back home, Virgil and Amy argue. He asks if she wants to spend her life with him if he is going to be blind forever. Amy hesitates, and Virgil decides to return home. Virgil eases back into his old way of life. While losing his sight, Virgil decides to look at as many things as possible, going through magazines and pictorial books in the library. He stays up to watch the sunset, seeing the horizon for the first and last time. After he has been blind again for some time, Virgil is at a park with a guide dog. Amy approaches and they reconnect. Amy apologizes to Virgil for trying to change him and for moving too fast. She asks if he wants to take a walk and "see what they see". They leave the park together.

Three young astronomers are baffled once the newest team member discovers radio signals of a seemingly impossible origin on 1420.163 MHz, in the water hole. After an unexplained power surge deletes crucial recordings, the team members unite and discover that the radio signals resolve to a response to the Arecibo message, a message beamed into space via radio waves in 1974, broadcast by a spacecraft in low Earth orbit using a cloaking system that renders the craft invisible on the visual spectrum but visible in infrared. After the team race to a local radio telescope array to get a new battery when a low battery threatens to halt their investigation, it turns out that the team were the first to receive and identify the message. At the finale, SETI coordinates a global message to be beamed to the craft: "Welcome to Earth", at which point the craft decloaks.