Once you've begun your final battle against the Resident Evil 5's final boss, Wesker, one of the first things you have to do is protect your partner. Use your rifle or a pistol to take some pot shots at the big guy to buy Sheva some time. Once she's safe, quickly rush to the end of the long rock outcropping to a giant boulder. Tap the action button quickly to have Chris shove the stone into the lava flow and create a land bridge.
Wesker will soon come and meet you at the center of the volcano. Although it might not be obvious, the easiest way to take him out is to blast away at the red/orange tumor on his back which is visible after he's done a whirling tentacle attack. After he's stunned from the

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damage, Chris can quickly launch himself onto him from melee range. Chris will tussle with him while Sheva finishes him off. It is possible to finish Wesker off by trying to destroy both weak points with your guns, although it is significantly more difficult.
Or if that's not your cup of tea, save a rocket launcher all the way to the end and blow him up real good. Either way, you'll win the game and go home a hero.