Let's take a look at what's supposedly killed him in the past:
1.
Tyrant ramming his claw through Wesker's gut. Okay, we all know he injected himself with the virus that Birkin gave to him and revived himself.
2.
The destruction of the Antarctic Base. We know he didn't die in his fight against Chris before this happened. Chances ae, he got out in time.
Now let's see what 'killed' him in Resi 5:
-
Overdose of the serum he needs to stop Birkin's virus going wrong, and then being hit by two Rocket Launchers (which looked to me as if they hit him directly, if not in the face) whilst being cooked in volcanic lava. Okay, even though I expected the volcano to somehow erupt just after the four get away, it doesn't seem possible that Wesker survived this one, and we know the Uroboros is sensitive to heat anyway. I would state that it wouldn't be a good idea to kill Wesker off as he's too central a character to the series, but apparently Resident Evil 6, according to Jun Takeuchi, will be a complete reboot of the franchise and I'm assuming that he means completely new storlines and characters, with the exception of remakes etc. Besides, when you look at it, each of the 'main' characters in the series has starred in one of the games at least twice.
Personally, I think Wesker's gone for good. The game seemed to signify that this time Chris would finally kill him.
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