Venlafaxine is a recently developed serotoninergic antidepressant whose reported toxicity at overdose levels includes central nervous system depression, seizures, and cardiovascular toxicity. The authors now present a case of venlafaxine overdose in a young woman complicated by a rise in plasma creatine kinase activity up to 52,600 U/L. Immediate therapy with intravenous fluids, bicarbonate, and furosemide was administered, and there were no further complications, notably no renal failure. This case supports the notion that venlafaxine can induce direct skeletal muscle toxicity leading to severe rhabdomyolysis. Therefore, clinicians should monitor muscle enzymes in patients with venlafaxine overdose to detect the development of rhabdomyolysis at an early stage and to initiate appropriate therapy rapidly.