Rosie O'Donnell has perfect response to Donald Trump after he slams her in presidential debate.

First, Hillary Clinton delivered some of the best smackdowns we’ve ever heard during the first US Presidential debate.

Now, actress and comedian Rosie O’Donnell has taken on Donald Trump (again) and reminded us why the business mogul should never be President.

While the 54-year-old proclaimed she wouldn't be watching the debate, when she heard that Donald Trump had once again brought up their long-running feud, she couldn't help but respond.

"The five mins orange anus can't seem to get over --- tell the truth - shame the donald," Rosie wrote on Twitter after the debate, including Hillary Clinton's hashtag, "#ImWithHer".

O'Donnell reminded her followers why Trump has such a vendetta against her, posting a video to a segment on The View where she sarcastically labelled Donald the "moral compass" for twenty-year-olds.

"This guy...he annoys me on a multitude of levels. Like he's the moral authority? Left the first wife, had an affair, left the second wife, had an affair, had kids both times...Donald, sit and spin my friend! I don't enjoy him, no," she said.

https://t.co/EvxYa7A4bL --- the 5 mins orange anus can't seem to get over --- tell the truth - shame the donald #ImWithHer

— Rosie (@Rosie) September 27, 2016

In response to her statements on the show, Trump called her a "real loser" and "a woman out of control".

"I'll most likely sue her for making those false statements...and it'll be fun. I look forward to taking lots of money from my nice fat little Rosie," he told People Magazine at the time.

The pair have famously been at each other's throats ever since.

During Monday night's debate, Hillary called out Trump's sexist comments.

"This is a man who has called women pigs, slobs, and dogs. Someone who has said pregnancy is an inconvenience to employers, and has said women don't deserve equal pay unless they do as good a job as men," she said.

Trump responded by referencing his long-running feud with O'Donnell.

"Rosie O'Donnell, I said very tough things to her, and I think everybody would agree that she deserves it and nobody feels sorry for her," he said.

Rosie also tweeted that she believed Trump would never win the election.

HE WILL NEVER BE PRESIDENT ... @WeinerAnne

— Rosie (@Rosie) September 27, 2016

Many other famous faces were also confused as to how Rosie O'Donnell was at all relevant to the Presidential debate.

Wait... did Trump whine about Rosie O'Donnell there at the end? Does he know where he is? Am I in the ninth circle of Hell?

— Seth MacFarlane (@SethMacFarlane) September 27, 2016

Mess with my girl Rosie and you're messing with me!!! Cruelty never made anyone a winner. ❤️ #rebelhearts4ever pic.twitter.com/gvkF6HpU47

— Madonna (@Madonna) September 27, 2016

You attack @Rosie, you attack us all #Donald. I've worked with @Rosie. @Rosie is #LOVE!

— Dustin Lance Black (@DLanceBlack) September 27, 2016

Nobody puts Rosie in the corner. #Debates

— Chelsea Handler (@chelseahandler) September 27, 2016

Watch Hillary Clinton answer 40 years of sexist questions.