"This does not come as a real surprise," said E! Online columnist Ted Casablanca. "He has always lurked in this gray area of his romantic life. He has always blurred the lines between his personal and professional lives. He has a history of marching to his own romantic beat."
Letterman married his high school sweetheart, Michelle Cook, in 1968, when he was just 21 years old. The couple divorced nine years later, just as Letterman's comedy career was starting to take off.
Just before he was named the host of NBC's "Late Night With David Letterman" in 1982, he began dating Markoe, who would become the show's head writer and who originated classic Letterman bits like Stupid Pet Tricks.
The couple reportedly stayed together for most of the 1980s. They were reunited on the air in 1994, when Markoe was invited to be a guest on Letterman's "Late Show" after he made the jump to CBS.
In a 1994 interview with USA Today, Markoe said, "It's not like Dave and I have no feeling for each other."
Letterman's relationship with Markoe may have led him to believe "that it was OK to have sex with the women who work for you," said Casablanca.
Markoe and Letterman regularly collaborated on ideas for the show.
"That was the nature of our relationship, a lot of goofing around," she told USA Today.
In typical Letterman fashion, he and Lasko were married in a secret ceremony on March 19, 2009 at the Teton County Courthouse in Choteau, Mont.
The couple already had a son together, Harry, in 2003. It was Letterman's first child.
"Regina and I began dating in February of 1986, and I said, 'Well, things are going pretty good, let's just see what happens in about 10 years,'" Letterman said in March when he announced their marriage from behind the same desk where on Thursday he admitted his affairs.
"He never felt pressured to get married. He had a longtime girlfriend that kept from the altar," Casablanca said.
"He was not one to give in to the romantic tradition, which is one reason people liked him," Casablanca added. "He's a rebel, but even rebels have to treat women kindly. You just get the sense that he so cavalier about it, that he thinks this is OK because it's him."
Given that multiple staff members seem to have been sexually involved with Letterman over an extended period of time, Casablanca surmised that it was likely known about among staff members and by Letterman's wife.
"Absolutely [Lasko] knew. You don't get in bed with Letterman in any sense, romantically or professionally, without knowing it's going to be a different set of rules," he said.
On Thursday, Letterman revealed to his audience that he received a package three weeks before containing a threat to reveal his indiscretions "if Letterman did not pay the individual a large sum of money" -- specified in a later communication as $2 million.
He said that the package contained a letter that said, "I know that you do some terrible things, and I can prove that you do these terrible things ... and sure enough what was contained in the package was proof that I do terrible, terrible things."
The audience laughed nervously as Letterman described how he'd called his attorney and then set up a meeting with his blackmailer in which the plotter told him he wanted to write a screenplay about him that included sordid details of the talk show host's life.