Waiting to Exhale is the story of four black women - Savannah Jackson, Bernadine Harris, Robin Stokes, and Gloria Matthews - residing in Phoenix, Arizona, in 1991. The women, who are all in their 30's, support each other through personal and professional challenges and successes. The women are savvy enough to manage every element of their lives, except finding fulfillment in love. The book's title stems from their collective anticipation of exhaling only when they have achieved satisfying relationships with a man.

The women think that they are doing everything possible to enact the change they seek in their lives, but stereotypes and bad habits seem to undermine their efforts. At the beginning of the novel, Savannah Jackson moves from Denver to Phoenix, because her friend, Bernadine lives there. Savannah has just landed a new job in Public Relations at a television station and has taken a pay cut just to leave the doldrums of living in Denver. Savannah's mother, whom Savannah substantially helps financially, does not understand why Savannah cannot find a man or a job that satisfy her.

Bernadine Harris has been married to her husband for twelve years, when he informs her that he wants a divorce so that he can marry his bookkeeper, who is a white girl. Bernadine is doubly wounded because of the sacrifices she has made to build her husband's business, and he has the audacity leave her for a white woman. The divorce process is more revealing than Bernadine could have ever imagined but she perseveres and successfully restructures her life.

Robin Stokes has a professional position is an insurance company but feels inadequate, because her intermittent boyfriend will not commit to marriage, and her father is dying from Alzheimer's, and she cannot afford better care for him and her mother. Robin's attempts to date other men are unsatisfactory, and she returns to her original lover. The relationship fails but Robin gains new hope for her future with an unexpected development.

Gloria Matthews owns a beauty shop catering to black women and is on the board of a civic organization that promotes black women in business and supports the causes of Black families in Phoenix. Gloria has a teenaged son from an unwanted pregnancy in college and tries to instill appropriate values in him so that he will not fall into the stereotype of so many black men, who abuse and abandon their wives and families. Gloria has buried her disappointment of years of unrequited love in food. Her weight problem becomes a serious health issue, which fortunately can be managed with a new outlook and love from a new neighbor.

At the end of the novel, each woman reaches a place of internal confidence in herself as a woman and as a friend to the other three, regardless of their individual circumstances and relationships with men.