Central to the Warhammer 40,000 universe are the Space Marines, somewhat anarchronistic combinations of genetically enhanced super-soldiers with world-destroying firepower, and crusading knights with an unswerving, fanatical loyalty to the God-Emperor. While Space Marines act as the special forces of the Imperium, the bulk of mankind's military power is found in the Imperial Guard, which consist of billions of regiments, each thousands of soldiers strong.Their quintessential opposition is the Chaos Space Marines, who betrayed the Emperor during the Horus Heresy, led by Warmaster Horus.

Much of the Milky Way Galaxy is controlled by the Imperium of Man, though it is not the only galactic power. Other races include the Orks, Eldar, survivors of an ancient fallen civilization reminiscent of classic fantasy Elves;the Tau, a young and technologically-sophisticated civilization of aliens that work for the greater good; the Necrons, soulless living metal constructs tricked into slavery by star gods; and the Tyranids, an all-consuming, all-organic, bio-engineered, extragalactic hive-swarm.Each of these races have playable armies. Other playable armies include the Witch Hunters and Daemonhunters, organizations within the Imperium, as well as the fallen Dark Eldar and the capricious Daemons of Chaos