Carnegie Mellon English Professor Lawrence Wetherhold (Dennis Quaid) is a depressed middle-aged widower. He is arrogant at work, uninterested in his students, and alienated from his two children. His adopted ne'er-do-well brother Chuck (Thomas Haden Church) arrives to borrow money and stay for a while, and tries to unwind Lawrence's lonely, high-achieving teenage daughter Vanessa (Ellen Page).
Meanwhile, Lawrence suffers a trauma-induced seizure after falling from the top of a fence in an attempt to retrieve his briefcase from inside of his impounded car. After being released from the hospital, Lawrence has a meeting with a sympathetic doctor, Janet (Sarah Jessica Parker), a former student he does not recall. Janet fulfills her long-ago crush with a "face-to-face" date with the professor, towards which Vanessa verbalizes her displeasure, confronting Janet about Lawrence's fragility. At dinner, however, Lawrence displays his stultifying arrogance and Janet walks out. The two reconcile at a second date, but, while spending the night, Janet is turned off by Lawrence's neediness and worries that he is, in fact, still too distraught by his wife's death. In order to get rid of him, she feigns being called in by the hospital and does not return any of his subsequent calls. On another night, in the midst of a contentious Christmas family dinner at the Wetherholds', Janet arrives unannounced with a cake.
After Chuck gets Vanessa drunk to celebrate her early acceptance into Stanford University, she makes a pass at him. He then moves in part-time with Lawrence's son, James (Ashton Holmes), in his college dormitory.
James' girlfriend and Lawrence's student Missy (Camille Mana) tells Lawrence that James has had a poem accepted at The New Yorker. By contrast, Lawrence has failed to sell his latest academic tome to any publisher. Vanessa changes the title to You Can't Read! and the book is sold to Penguin Group, a large non-academic publisher in New York. To Lawrence's dismay, however, the book is largely re-worked and edited by the publisher. Janet accompanies him on a trip to New York, where she learns she is pregnant by Lawrence. Pre-occupied by his book publishing and an on-going campaign to become chairman of the English Department at the college, Janet is again upset by Lawrence's self-absorption and breaks up without telling him the news.
Back in Pittsburgh, Lawrence is additionally confronted by both James and Chuck, who both point to his uninvolvedness with his children's lives. Helped along by Chuck, Lawrence goes to the hospital to reconcile with Janet, who reveals her pregnancy. He has meanwhile become a more involved parent and professor. During the end credits, the main characters cradle twin babies.