The Island Of The Crazies is the second-last mission in the

Impossible Creatures campaign, and is set on the island of Isla Inasnum. Upton Julius uses the island as a dumping ground for his failed experiments. The island is infected with a virus that only affects combined creatures, driving them insane(giving the island its name) and then killing them. Dr Ganglion deliberately tells Rex about the virus, but only after they have landed, as Rex is also affected by the virus.

The player must cure Rex by getting him to a nearby chamber containing the antidote in less than 15 minutes. All of the player's combined creatures must be cured as well, or they will lost control of them and the creatures will attack them. After Rex has been cured, the player must destroy the base of the Insanum Custodians, as he aims to remove every trace of the Sigma Technology.

The player may use Rex to collect genetic samples of the Elephant, Great White Shark and Sperm Whale on this island, but these are not necessary to complete the mission.