Once, only telepaths could use Cerebro, but Shadowcat modified the machine a few years ago so that anyone with proper security clearance could use it. It still performs best when used by Professor Xavier or a being with similar telepathic abilities. By wearing a special headset connect to Cerebro, Xavier is able to use his psionic powers to increase Cerebro's ability to detect prionic waves. Indivdual members of the X-Men have sometimes carried smaller versions of Cerebro colloquially termed "portable Cerebros" with them. A "portable Cerebro" in telemetric with the main computer console, can detect the presence of a human mutant at short range.

Xavier began work on developing Cerebro before he founded the X-Men. He used an early version of the device, he called Cyberno to locate Scott Summers, who, as Cyclops, became Xavier's first recruit for the X-Men. Xavier completed the first true Cerebro machine shortly after the fifth X-Man, Marvel Girl (Jean Grey), joined the team. He named Cerebro after the human cerebrum, the largest section of the human brain and the part responsible for transmitting waves.

Cerebro is outfitted with security measures as well, being set up for only certain people with proper security clearance to use. This is enforced through the finger pads (reconfigurable for other races) which conduct expressive body-field measurements that identify individuals. The Lo-Res antenna info plus the finger field sensor input is monitored throughout Cerebro use- any irregularities could be a sign of deception or psi intrusion.