Melee in Duke Nukem Forever involves punching or buttstroking with the player's weapon. It deals 30 points of damage per blow.
Occasionally, an enemy may fall to its knees when it is about to die. In these moments, Duke can perform an "execution," in which he delivers the final blow. Executions instantly refill the player's ego to maximum capacity.
- One of Duke's many quotes when killing an alien is, "I'm from Las Vegas, and I say kill 'em all!" This is a reference to Starship Troopers, in which Johnny Rico says the same line but with "Buenos Aires" instead of "Las Vegas."
- When performing an execution, Duke will sometimes utter, "There can be only one." This is a quote from Highlander.
- Another of Duke's many quotes when killing an alien is, "Good, bad, I'm the guy with the gun." This is a quote by Bruce Campbell in Army of Darkness.