This is the hardest achievement in the game and requires you to play through the whole single player campaign on Level 4 difficulty or harder. I suggest a lot of practice before attempting this since enemies are significantly harder than on the lower difficulties.
The final boss is Xaeros. Be careful when he possesses a rail gun since he has 99% accuracy with it. Your best bet is his stupid AI. He will keep dropping to his death, thus making it easier for you to win. I recommend you to get the BFG10k to try and kill him right after he spawns and prevent him from getting his rail gun.
Right after you've beaten Xaeros, the achievement will unlock.