Doctor Alexander Roland Isaacs, played by Iain Glen, is the main antagonist of the Resident Evil series, though this is not known until Resident Evil: The Final Chapter.
One of the two founders of the Umbrella Corporation, Isaacs was the true mastermind behind the release of the T-Virus as revealed in The Final Chapter, planning to wipe the world clean of humanity and repopulate it with the Umbrella elite kept in cryogenic stasis in The Hive beneath Raccoon City. Isaacs murdered his partner Dr. James Marcus and raised Marcus' daughter Alicia who inherited her father's half of the company, allowing him to control it and her.
In Resident Evil: Apocalypse, Isaacs, later revealed to be a clone, experiments upon Alice and Matt Addison in flashbacks, transforming Matt in the Nemesis. He later revives Alice after she dies in a helicopter crash following the destruction of Raccoon City and enhances her powers. When Alice escapes the facility, Isaacs lets her go and activates "Program: Alice".
Five years later in Resident Evil: Extinction, Isaacs hunts for Alice in the post-apocalyptic wasteland of North America while performing experiments using Alice's blood and clones of her in an attempt to find a cure for the T-virus. Isaacs' experiments create the Super Undead which he unleashes upon Claire Redfield's convoy in the ruins of Las Vegas while trying to simultaneously capture Alice. After his efforts fail, Isaacs flees back to base, but not before getting bitten by a Super Undead. Despite taking massive quantities of the anti-virus, Isaacs mutates into a creature with near-invulnerability and telekinetic abilities that surpass Alice's own. Isaacs slaughters the Umbrella staff and battles Alice through the recreation of the Hive. In a final confrontation in the Laser Corridor, Isaacs is destroyed when an Alice clone takes control of the laser grid and uses it to slice him to pieces. This particular clone appeared to be more of an employee of the company, working as virologist and subservient to Albert Wesker, closer in nature to the clones of Alice's allies used as shock troopers in Resident Evil: Retribution than the clone that would later appear in The Final Chapter.
In Resident Evil: The Final Chapter, after being captured by an Umbrella convoy leading an army of Undead to Raccoon City, Alice is shocked to find it commanded by Isaacs, having thought him dead years before. Isaacs uses human captives dragged behind the tank to lure the Undead to follow him. Alice quickly realizes that the Isaacs she previously fought was just a clone with Isaacs telling her that he was awoken from stasis to finish leading the destruction of humanity. Alice eventually manages to escape, chopping off Isaacs' hand in the process. Isaacs leads his army against the last human settlement in the ruins of Raccoon City, but Alice commands an effective defense, destroying the army and Isaacs commandos. Isaacs himself manages to escape, and takes command of another Umbrella army, slaughtering a tank crew and leading the army into the crater leading to the Hive in an effort to stop Alice once and for all.
In the Hive, Alice encounters another Isaacs, awoken by Wesker, who reveals himself to be the real Alexander Isaacs and the one Alice encounter in the convoy to be a clone who was unaware of his true nature. The real Isaacs has technological upgrades that give him an advantage against Alice, predicting her every move. Isaacs reveals Alice's own true nature as a clone of Alicia Marcus and his plan to kill both Alice and Alicia which will give him full control of Umbrella. Alicia uses her fifty percent control of Umbrella to fire Wesker, allowing the Red Queen, allied with Alice, to crush Wesker's legs with a door. Isaacs flees with the anti-virus that can stop the T-virus once and for all and shuts the Red Queen down so that she can't help Alice anymore. Isaacs proves to be more than a match for both Alice and Claire Redfield, slicing off three of Alice's fingers in the Laser Corridor, but being apparently defeated when she places an activated grenade in his pocket at the same time. Isaacs life support system revives him in time to stop Alice from releasing the anti-virus, but he is then confronted by his clone. In an ironic twist, Isaacs is stabbed to death by his own clone when the clone can't accept that he isn't the real Isaacs, a piece of programing in the clones that Isaacs had earlier found amusing. The Isaacs clone is killed by his own Undead army, allowing Alice to retrieve and release the anti-virus as the Hive is destroyed by explosives she planted. The destruction of the Hive and the Umbrella elite within cements the end of Umbrella and Isaacs plan while the Red Queen is able to reactivate herself once Isaacs is dead and call off the Umbrella attack on the remaining human settlements.