Spoiler warning for... oh, forget it. This is the worst-kept secret since...well, ever.
Spider-Man is dead.
Wait a minute, you say. No, he isn't. I read Amazing Spider-Man #545. That isn't what happened.
Well, maybe you misread it. Peter Parker gave up. He surrendered to the Marvel universe's Ultimate Evil and gave him permission to rewrite his life retroactively, potentially remove him from existence completely (Mephisto hinted he could do that), counting on the Ultimate Liar to be telling the truth just this once, that in return for doing so Aunt May would live.
It would be just like Mephisto if Pete returned to the old homestead and found Aunt May alive as a disembodied brain in a jar on the mantel.
See ya later, Joe. Or not.