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Quake 4 is the true sequel to Quake II, continuing the Strogg vs. Humans storyline from the point where Quake II ended. The Strogg is an alien cyborg race which, much like the Star Trek Borg race from which they seem to be partly inspired, wander the galaxy conquering planets and wiping civilizations. Their sole purpose is to collect organic body parts with which to swell their ranks. After a prolonged war, the united armed forces of Earth decided to launch a desperate counter attack on the home planet of the invaders, Stroggos. By some twist of fate a sole marine was able to disable the Strogg main planetary defense (aka The Big Gun) and kill Makron, their leader. That was the end of Quake II. The second wave of attack is meant to land on Stroggos and take advantage of the brief disorder, ending the threat of the Strogg forever. Of course it will not be that easy...

This time the lone soldier theme (of Quake I, II and the Doom series) is replaced by a war. Not as large scale as a military FPS or even Halo, but close enough. There are squad mates, some of which are important to protect, some vehicles (a hovertank and a mech) and frequently changing objectives to achieve. The arsenal contains elements from all Quake games (nailgun, rail gun, lightning gun) and the classic BFG has been replaced by the Dark Matter Gun. Weapons can be improved later in the game, making them much more effective. The game uses a somewhat improved version of the Doom 3 engine to good effect. Multiplayer options are rather limited, offering only the standard Deathmatch modes and CTF.

Quake 4 was developed by Raven under the guidance of id Software.