After her young son is killed in a car accident and her husband, a surgeon, admits during sex to having had an affair, the protagonist Claire Newbold – a successful medical sales representative in her early forties – fails to return home from a business trip.

Reviewers Joanne Kaufman and Betsy Kline liken the novel to other fiction of the 1990s in which a woman leaves her life and family behind, including Anne Tyler's Ladder of Years (1995), Kathryn Harrison's Exposure (1993) and the short story "Crocodile Tears" by A. S. Byatt (anthologized in 1998).

[6][10] The novelist Karen Karbo, reviewing the novel in The New York Times, writes: With '"Layover," Zeidner joins the ranks of Doris Lessing, Margaret Atwood and Fay Weldon, all of whom have written in the women-spiraling-into-madness genre.

[11] In a review for the Chicago Tribune, Kaufman writes: "The considerable strength of "Layover" can be measured in the willingness of readers to give Claire the rights and privileges and emotional rope they'd probably withhold from others."

"[10] The Publishers Weekly review praises the novel's unusual approach to the theme of long-term grief, and states that in addition to the "titillating—and sometimes funny" sex scenes it presents a sharply satirical view of society, that deconstructs those men whose work supplies "a false sense of aggrandizement" as well as their female partners.

[13] A review in Library Journal recommends the novel, describing Claire's course as "oddly appealing, even familiar to any reader caught in the absurd quests demanded by midlife.

"[14] Betsy Kline, in a review for the Pittsburgh Post-Gazette, writes that Layover "dares to poke holes in the surface of polite grief and allow an intelligent women free rein of a consuming pain, descending to levels of larceny and lust that are both chilling and, at times, exhilarating to behold.

"[6] Martin Wilson, in a review for The Austin Chronicle, praises the novel's "humor, wisdom, and poignancy" and its "compelling, sometimes hilarious" narrator; he states that a strength of the work is its emphasis on the notion that redemptive endings require effort and might not always be achievable.

In an analysis of why the novel succeeded, Maass writes that Zeidner dug deep, and as a result Claire Newbold achieves a kind of Everywoman depth and power.

Emotional appeal, a rare-but-credible decision to drop out and the conflict inherent in a married woman plunging into a mind-numbing, soul-freeing bout of sex all combine to make a breakout premise.