Soon after video of Rendell making the comment hit the Internet, bloggers pounced, reading into his words not just a sexist subtext but, as psychologist Bella DePaulo put it, a smattering of "singlism."
"The interesting thing about 'singlism' is that it is often the most achieving women who get the most put down," said DePaulo, a professor of psychology at the University of California at Santa Barbara and author of "Singled Out: How Singles Are Stereotyped, Stigmatized, and Ignored, and Still Live Happily Ever After."
CNN commentator Campbell Brown Wednesday suggested Rendell's comments were sexist and said they "perpetuate stereotypes that put [women] in boxes."
Feeling the heat, Rendell tried to step back away from his comments, telling the Philadelphia Inquirer Wednesday: "What I meant is that Janet is a person who works 24/7, just like I do. She has no life. Neither do I."
But that comment only dug the hole deeper, said Kathleen Jamieson, professor of political communication and director of the Annenberg School for Communication at the University of Pennsylvania.
"Just because someone is single doesn't mean they don't have a life outside of work," said Jamieson. "If his assumption is that someone with a family wouldn't be good at the job, then that's a problem too.
"There is no way to parse his sentence that makes it in any way intelligible. He is either making assumptions about women and child-rearing that are obsolete, or he is somehow suggesting the opposite. Is he somehow less effective because he has raised a family?"
Napolitano, 51, is not the only unmarried woman joining the Obama administration.
Melody Barnes, 44, a member of Obama's team of economic advisors has been tapped to serve as director of the Domestic Policy Department and is unmarried. Stephanie Cutter, 40, an Obama spokesperson is also unmarried.
Condoleezza Rice, 54, is perhaps the most prominent single woman in American politics.
Though Rice rarely talks about her personal life, Beltway insiders routinely gossip and speculate about whom she is dating.
When asked by CNN's Wolf Blitzer for "an anecdote, a story something you learned about Condoleezza Rice in researching this book … maybe the most fascinating little nugget," New York Times correspondent Elisabeth Bumiller, the author of a biography of Rice, talked about the secretary's fondness for dating football players.
In Bill Clinton's Cabinet, both Donna Shalala, the secretary of health and human services, and Janet Reno, the attorney general, were unmarried women.
Reno was routinely mocked on "Saturday Night Live" and portrayed as mannishly tough by a male actor.
There are currently in Congress about 50 unmarried or divorced members and 12 more who are widowed -- roughly 15 percent of Congress, according to the newspaper The Hill.
DePaulo said both single men and women are discriminated against, but that women, especially those who have risen to prominence, are particularly, well, singled out.
In a 2004 interview with then Green Party candidate Ralph Nader, MSNBC's Chris Matthews asked how Nader could accuse Bush of being irresponsible when "he's raised two daughters; he's had a happy marriage. Isn't he more mature in his lifestyle than you are?"
"We hear more about women. They get it much worse. Single men are called bachelors, which doesn't sound that bad, but single women are called 'spinsters' and 'old maids,'" DePaulo said.
"We tell women they need to get married because 'your work won't love you back' and 'your eggs will dry up.' We also look at single women as extra promiscuous, basically sluts," DePaulo said.
DePaulo attributes some "singlism" to jealousy.
Married people, she said, want to buy into the idea that their spouses somehow make them more complete. "When they see single people just as accomplished and just as happy it rattles them," she said.
Despite the stereotype that singles are freewheeling individuals without any attachments, DePaulo said the research proves the opposite.
"In several national surveys, what's been found is that it's single people more than married people maintaining connections with friends, neighbors, siblings and parents. More than married people, its singles who do more work of connecting with other people."