when someone is being bothered by another person and is starting to get really pissed off and wants them to just go away or shut up
Jon: Yo give me $2.50 for lunch, I have no money.
Jon: Please yo, don't be a fag, I'm hungry
Chris: Fuck off Jon!
It's another way of saying "for God's sake" but usually used if your pissed or frustrated about something.
Chris: Where's Rich?
Marcus: He's still inside.
Chris: For fuck sakes! Call him out, we're already late.