Instead of sticking with formality and shaking Trump's hand, Clinton merely nodded in his direction, saying, "Hello."
The candidates eventually shook hands at the end of the debate, after an audience member asked them to "name one positive thing that you respect in one another."
Although co-moderator Marta Raddatz of ABC News offered Trump the opportunity to answer first, Clinton jumped in instead, complimenting Trump on his children.
"His children are incredibly able and devoted and I think that says a lot about Donald," Clinton said.
During his turn, Trump thanked Clinton for her kind words about his children, who were in the audience. He then said of Clinton, "She doesn't quit and doesn't give up."
"I respect that," Trump said. "She is a fighter."
Tonight marked the first time Trump and Clinton came face-to-face after the release of a videotape Friday in which Trump can be heard making lewd comments about women.
"And when you’re a star they let you do it...you can do anything," Trump said in the 2005 video while speaking to former "Access Hollywood" host Billy Bush.
"Whatever you want," another voice chimes in.
"Grab them by the p----," Trump says. "You can do anything."
Trump chalked up the comments to "locker room banter."