The novel shifts back and forth through the late 20th century, intermittently following spouses Alfred and Enid Lambert as they raise their children Gary, Chip, and Denise in the traditional Midwestern suburb of St. Jude, and the lives of each family member as the three children grow up, distancing themselves and living on the East Coast. Alfred, a rigid and strict patriarch who worked as a railroad engineer, has developed Parkinson's and shows increasingly unmanageable symptoms of dementia. Enid takes out her frustrations with him by attempting to impose her traditional judgments on her adult children's lives, to their annoyance.
The middle son, Chip, is an unemployed academic living in New York City following his termination as a tenure-track university professor due to a sexual relationship with a student. Living on borrowed money from Denise, Chip works obsessively on a screenplay, but finds no success or motivation to pay off his debts. Following a rejection of his screenplay, Chip takes a job from his girlfriend's estranged husband Gitanas, a friendly but corrupt Lithuanian government official, later moving to Vilnius and working to defraud American investors over the Internet.
Their eldest son, Gary, is a successful but increasingly depressive and alcoholic banker living in Philadelphia with his wife, Caroline, and their three young sons. When Enid attempts to persuade Gary to bring his family to St. Jude for Christmas, Caroline is reluctant, and turns Gary's sons against him and Enid, worsening his depressive tendencies. In return, Gary attempts to force his parents to move to Philadelphia so that Alfred may undergo an experimental neurological treatment that he and Denise learn about.
Also living in Philadelphia, their youngest child Denise finds growing success as an executive chef despite Enid's disapproval and persistent scrutiny of her personal life, and is commissioned to open a new restaurant. Simultaneously impulsive and a workaholic, Denise begins affairs with both her boss and his wife, and though the restaurant is successful, she is fired when they are uncovered. Flashbacks to her childhood show her responding to her repressed upbringing by beginning an affair with one of her father's subordinates, a married railroad signals worker.
As Alfred's condition worsens, Enid attempts to manipulate all of her children into going to St. Jude for Christmas, with increasing desperation. Initially only Gary and Denise are present, Gary having failed to convince his wife or children, while Chip is delayed by a violent political conflict in Lithuania, eventually arriving late after being attacked and robbed of all his savings. Denise inadvertently discovers that her father had known of her teenaged affair with his subordinate, and had kept his knowledge a secret to protect her privacy, at great personal cost. After a disastrous Christmas morning together, the three children are dismayed by their father's condition, and Alfred is finally moved into a nursing home.
As Alfred's condition deteriorates in care, Chip stays with Enid and visits his father frequently while dating a doctor, eventually having twins with her. Denise leaves Philadelphia and moves to New York to work at a new restaurant where she is much happier. Enid, freed of her responsibilities and long-time frustrations with Alfred, slowly becomes a more open-minded person, and enjoys a healthier involvement in her children's and grandchildren's lives, finally stating that she is ready to make some changes in her life.
