Nine people in Baltimore deal with their respective romantic problems, usually thwarted by the differing ideals and desires of their chosen partner. At the center of this is Gigi Phillips (Ginnifer Goodwin), a young woman who repeatedly misinterprets the behavior of her romantic partners.
Gigi and Alex[edit]
Gigi (Ginnifer Goodwin) is a single woman who repeatedly misreads mundane actions and comments from her dates as indications that they are romantically interested in her, and frets when the guy does not call her.
In attempting to meet Conor Barry (Kevin Connolly), a real estate agent, at a bar, she befriends the bar owner Alex (Justin Long), who reveals the strategies men use to avoid a woman. He explains that if a man is interested in a woman, he will overcome any obstacles to ensure they date again, and that Gigi has been misinterpreting and obsessing over imagined "signs" that she receives. Their friendship continues, and Gigi interprets his eagerness to always assist (such as taking Gigi's call while he is on a date) as a sign that he is interested in her. She makes a move, but Alex claims he is not romantically interested in her and chastises her for ignoring his advice. She angrily replies that at least she has not let herself become cynical and bitter like him.
Gigi eventually moves on from Alex, however, in a role reversal, Alex begins falling for Gigi. After leaving several unanswered messages, Alex arrives at Gigi's apartment to declare his love. Gigi thinks that she is the rule, but after Alex suddenly kisses her passionately, he says that she is his exception.
Janine, Ben, and Anna[edit]
Gigi's friend and co-worker Janine Gunders (Jennifer Connelly) is having difficulties in her marriage to Ben (Bradley Cooper). As Janine obsesses on their home renovations, Ben becomes attracted to Anna Marks (Scarlett Johansson), a yoga instructor and aspiring singer, and the feeling is mutual. Ben and Anna pursue a flirtatious friendship under the pretense of him helping her establish a singing career. Ben reveals to Anna that Janine once gave him an ultimatum by threatening to leave him if he did not propose. Ben agrees to be friends with Anna, and in order to flirt with him she strips and jumps naked into a swimming pool. She invites him to join, but he decides against it.
Fervently anti-smoking (due to her father's death from lung cancer), Janine pointedly asks Ben if he has been smoking and later is perturbed to find cigarette butts hidden in their back yard. Ben insists that they are not his, and their contractor, Javier (Luis Guzman), says none of his workers smoke at the house. During a tense shopping trip, Ben reveals to Janine that he has cheated on her. Janine is devastated but rationalizes Ben's behavior, blaming herself for being too cold in the relationship, and decides she wants to save their marriage.
After a positive meeting about her singing career, Anna begins to have sex with Ben in his office. They are interrupted by Janine who, hoping to spice up their marriage, has arrived unexpectedly. Anna hides in a closet, and Ben attempts to send Janine away who then makes a heartfelt plea to save their marriage, and there are indications she succeeds in seducing him. After Janine leaves, Anna angrily departs vowing to cut ties with Ben. As Janine tidies up Ben's clothes back at their completed house, she discovers a fresh pack of cigarettes in a pocket, and she explodes in anger. When Ben returns home, he finds his clothes neatly folded with a carton of cigarettes and a note attached from Janine asking for a divorce. Janine moves into a new apartment by herself to start a new life, and Anna is later seen performing at an upscale nightclub. Ben is alone, purchasing the same beer at the same supermarket where he met Anna.
Conor, Anna, and Mary[edit]
Meanwhile, Anna enjoys a close friendship with Alex's friend, Conor. He is romantically interested in her, but Anna is only interested in a casual relationship. Conor misinterprets her hugs and cute nicknames for potential romantic interest.
Anna's friend, Mary Harris (Drew Barrymore), works in advertising for a local newspaper, and helps Conor promote his real estate business in a series of print ads. Like Gigi, she meets many men (mostly online), but despite constantly monitoring emails, pager, phone, and Myspace messages, her dates go nowhere.
While Conor attempts to cultivate a gay clientele, two gay men tell him how he is going wrong with Anna. Taking their advice, Conor decides to declare his love to Anna. Vulnerable after falling out with Ben, Anna agrees to start a serious relationship with him. But when Conor proposes buying a house and moving in together, Anna admits she doesn't want to, and they break up.
Mary later runs into Conor, recognizing him from his ad photo, and introduces herself, since they have only spoken over the phone. They hit it off, and start dating.
Beth and Neil[edit]
Gigi's other co-worker, Beth Murphy (Jennifer Aniston), is living with her boyfriend, Neil (Ben Affleck), who is also friends with Ben. After seven years of dating, Beth wants to get married, but Neil does not believe in marriage. With Gigi's newfound pragmatic stance on relationships after advice from Alex, she announces she will no longer misinterpret vague gestures from men as more than they really are. This spurs Beth to confront Neil about their relationship. When he still doesn't want to get married, she breaks up with him.
Later, the preparations for her younger sister's wedding brings the issue into sharper focus for Beth after hearing many back-handed comments from various family members. During the reception, her father Rod (Kris Kristofferson) suffers a heart attack. Beth looks after him as he recuperates while her sisters wallow, and their husbands remain glued to the television playing video games and watching football with constant takeout as the household falls into chaos. As Beth reaches the end of her patience looking after her siblings and in-laws as well as her recovering father, Neil arrives with groceries and helps with the chores. The two reconcile, with Beth saying that Neil is more of a husband to her than her sisters' spouses are to them, and she will not insist they be married. Neil later proposes to her, and they marry in an intimate ceremony aboard his sailboat.
Who interrupts Anna and Ben while they're having sex?
Janine