Keyes became known for her novels Watermelon, Lucy Sullivan Is Getting Married, Rachel's Holiday, Last Chance Saloon, Anybody Out There, and This Charming Man, which, although written in a light and humorous style, cover themes including alcoholism, depression, addiction, cancer, bereavement, and domestic violence.

During this period she became an alcoholic and was affected by clinical depression, culminating in a suicide attempt and subsequent rehabilitation in 1995 at the Rutland Centre in Dublin.

[4] Keyes appeared on BBC's Imagine, aired in February 2022,[5][6] explaining to Alan Yentob how she was distracted from her resolved end-of-life attempt by an episode of Come Dine With Me; husband and assistant Tony defused the drama by saying, "let's see how you feel when we've finished watching it," and so began her slow recovery from depression.

During this time she also wrote The Mystery of Mercy Close, a novel in which the heroine experiences similar battles with depression and suicide attempts as those Keyes herself experienced.

[2] During her appearance on the show, Keyes also told host Kirsty Young that in spite of all her efforts to treat her depression, including cognitive behavioral therapy, medication, mindfulness, hospitalisation and diets, what finally healed her was time: "It was an illness and it ran its course.

Keyes lives in Dún Laoghaire with her husband Tony Baines (whom she first met on his 30th birthday[5]) after returning to Ireland from Hampstead in 1997.

[5] Although many of her novels are known as comedies, they revolve around dark themes, often drawn from Keyes's own experiences, including domestic violence, drug abuse, mental illness, divorce and alcoholism.

[4] Keyes' stories usually revolve around a strong female character who overcomes numerous obstacles to achieve lasting happiness.

[11] In an interview with The Irish Times in 2017, Keyes announced that she suspected "gender bias" to be at play when it comes to the recognition of women writers.

"Do you remember in the early noughties when a lot of Irish women writers like Cathy Kelly, Sheila O'Flanagan, Cecelia Ahern were selling all over the world?