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The Sentinel robots were created by noted anthropologist Doctor Bolivar Trask, who intended to use them to save humanity from mutants. During a televised debate between Trask and Professor Charles Xavier, Trask revealed their existence and activated the robots. Xavier and Trask were soon kidnapped by the rogue Sentinels and brought to their Master Mold. The X-Men arrived and with the help of Trask, seeing the error in his assumption that all mutants were a threat.

Bolivar's son Larry built the Mark II Sentinels in an attempt to carry out his father's original purpose. Larry had previously been given a medallion by his father to block the Sentinel's from sensing his mutant genes. Trask, unaware of his lineage removed it, and was slain by his creations. Fortunately, the second generation Sentinels were tricked into flying into the sun by Cyclops.

The Asgardian trickster god Loki later magically merged three Sentinels into the massive Tri-Sentinel, and sent the robot to destroy New York City by destroying the nearby nuclear power plant. Spider-Man, aided by the Uni-Power, became Captain Universe, and succeeded in destroying the Tri-Sentinel before in could carry out Loki's endeavor. However, the Tri-Sentinel's remains were gathered by a survivalist group, and rebuilt itself once again attempting to destroy the power plant, but was destroyed on a sub-atomic level by Spider-Man, with the help of Nova (Richard Rider).

Project: Wideawake, a government agency headed by Henry Peter Gyrich, purchased Sentinels built by Sebastian Shaw, the mutant Black King of the Hellfire Club. Wideawake also attempted to recreate Nimrod, an advanced Sentinel that had traveled back in time from Rachel Summers' timeline.

The Dark Beast, in the service of the psychic entity called Onslaught, reprogrammed a number of government-owned Sentinels. These Sentinels were opposed by the combined forces of the X-Men, the Avengers, and numerous other heroes. They also killed the parents of Hallie Takahama (Jolt), and permanently damaged Green Goblin (Phil Urich)'s equipment, forcing him to retire.

In the events of Operation: Zero Tolerance, a number of humans were transformed into cyborg hybrids known as Prime Sentinels. These Sentinels were led by the robotic humanoid Bastion. The Prime Sentinels succeeded in capturing many of the X-Men. However, the President was convinced by Senator Robert Kelly and Gyrich to suspend Bastion's operations and he was captured by S.H.I.E.L.D.. Karima Shapander, one of the Prime Sentinels, subsequently had her mind restored by Magneto and Xavier.

In the war against Kang, a squadron of Sentinels was sent to attack his space station. Kang, however, with his advance knowledge of robotics, easily gained control of the Sentinels and sent them back to Earth. During the course of the war, the robotic hero Machine Man was temporarily reprogrammed with Sentinel programming by Bastion.

Cassandra Nova, Professor Xavier's twin sister, convinced the last living relative of Bolivar Trask, Donald Trask III, to activate an abandoned Master Mold in Ecuador. Cassandra duplicated Trask's DNA so she could issue orders to the Sentinels, then used the Master Mold to send two massive, highly adaptive "Wild" Sentinels to destroy the mutant homeland of Genosha, killing over 16 million mutants. One of these Wild Sentinels was later given a conscience by Danger.

Nova also programmed a number of microscopic, nanite-based Nano-Sentinels to attack the blood cells of the inhabitants of the Xavier Institute, with which infected herself with just as she was captured by Cyclops and Wolverine. The Nano-Sentinels were all destroyed by Xorn except the Sentinels used to restore Professor Xavier's spine and legs.

A deactivated Sentinel was discovered by Juston Seyfert, who rebuilt and reprogrammed it in an attempt to give himself a better life. After the CSA discovered his Sentinel, Juston decided to run away and use the Sentinel's DNA Detection skills in an effort to find his mother, who abandoned him.

In the aftermath of House of M|"M-Day", the Office of National Emergency (O.N.E.), a branch of the Department of Homeland Security, had Sentinels instituted at the Xavier Institute to watch over the X-Men. Many X-Men were uncomfortable with this, particularly, Rachel Summers, who considered it a real-life reminder of the anti-mutant future she originates from. This group of Sentinels is unique in that they are piloted armors. The current Sentinel Squad O*N*E was built with the aid of Tony Stark and trained by Jim Rhodes, the former War Machine.

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- Marvel Editorial Staff