We report three cases of compartment syndrome in the thigh related to drug intoxications. Compartment syndrome is an uncommon condition often diagnosed late as it may occur in unconscious patients. The typical clinical presentation begins with pain of the lower limb refractory to major antagesics. The condition then progresses with sensoromotor involvement of the sciatic nerve. Rapid onset of acute renal failure in the setting of a crush syndrome may be life-threatening with a long-term risk of major sensoromotor sequelae. Surgical treatment with aponeurotomy is required rapidly to limit sequelae.