Aurora (Shirley MacLaine) and Emma Greenway Horton (Debra Winger) are mother and daughter, both searching for deep romantic love. Beginning with Emma's early childhood, Aurora reveals how difficult and caring she can be by nearly climbing into Emma's crib in order to make sure her daughter is breathing—only to be reassured once Emma starts crying (after physically waking her up). The two have an extremely close love-hate mother/daughter relationship as Emma grows up.

The film follows both women across several years as each find their reasons for going on living and finding joy. Emma gets married immediately upon graduating High School in the Houston area, while her best friend Patsy (Lisa Hart Caroll) continues on to college, eventually becoming successful and rich in New York City. Emma has two children that she and her husband, college professor Flap Horton (Jeff Daniels), struggle to support in Des Moines, Iowa, and she later telephones her mother and asks for money when she is pregnant with her third child. Aurora, not knowing by the telephone call that Emma is already several months pregnant, wants Emma to get an abortion. Emma's once-passionate marriage to Flap becomes strained, thanks mostly to his philandering, and she finds a lover in small-town, older banker Sam Burns (John Lithgow), with whom she eventually has a romantic love affair as well.

At the same time, Aurora cultivates the attention of several gentlemen in the area, some rather bizarre, but is attracted to her next door neighbor of fifteen years, the philandering, retired astronaut Garrett Breedlove (Jack Nicholson). Garrett has been drinking heavily for years and partied with very young women at his home. Aurora and Garrett eventually go on a lunch date, make love and develop a tenuous relationship. One scene shows them speeding in his open Corvette convertible along a quiet beach as he recklessly sits on top of the car and steers with his foot.

Emma returns to her mother's home in Houston after discovering her husband is having an affair with a young grad student named Janice, who attends the same college where Flap teaches. However, Emma's appearance along with her three children spooks Garret, who has been single for a long time. After re-assessing his relationship with Aurora, Garret breaks up with her, greatly upsetting Aurora. While Emma is in Houston, Flap telephones her and she reluctantly returns home to Iowa, attempting reconciliation with him. Both accept that they have each made mistakes.

Emma ends the relationship with Sam after Flap accepts a new teaching position in Kearney, Nebraska. Although she does not want to, Emma agrees to relocate to further Flap's career. However, Emma soon discovers that Janice is attending the same college where Flap now works, realizing that Flap followed her to Nebraska. With her daughter in a stroller, Emma confronts Janice before taking her daughter to the doctor's office so both can get flu shots. While administering the injection, Emma's doctor notices two large lumps under her armpit. Although Emma is only in her 30s, the doctor orders a biopsy and discovers she has a "malignancy."

Emma's childhood friend Patsy invites her to New York City for her first vacation without her children. However, after arriving, Emma feels out-of-place amongst Patsy's friends and returns home early to begin treatment for her illness. Later, her doctor informs her that the drugs she was taking did not "have the desired effect," and that she will not survive her illness. Flap and Aurora remain by her bedside in the hospital for weeks. Although devastated and exhausted, Aurora is still very supportive and loving towards Emma. Garrett flies to Lincoln, Nebraska and surprises Aurora, and the two proclaim their love for each other.

After a discussion in the hospital cafeteria between Aurora and Flap, in which Aurora tells him he doesn't have the energy for a job, chasing women, and managing a family, Aurora tells Flap she will raise his and Emma's children in Houston. Although Patsy, who has no children of her own, wants to adopt Melanie, Flap and Emma do not want their children to be separated. Emma, not wanting Janice to raise her children and Flap, feeling like a failure as both a father and a husband, agree that living with Aurora is best for their children.

As Emma's time begins to run short, Tommy shows open resentment toward his mother due to circumstances such as social class, fights between his parents, and Tommy's perception of feeling unloved. Emma reassures all three children they are loved, and after an altercation with Aurora, Tommy weeps in her arms. Emma dies later that night. Following Emma's funeral, Emma and Aurora's friends and family gather in Aurora's back yard for a wake. Garrett shows love toward each of Emma's children and helps Tommy cope during the wake. The film closes on Aurora, holding her grandchild Melanie.

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