Antihistamines, which are readily available over the counter in sleeping aids, are commonly found in intentional overdoses. We report three new cases of severe rhabdomyolysis related to ingestion of these agents. This is a rarely reported but potentially overlooked complication among patients who present to the emergency center after intentional overdoses. We also describe the potential mechanism of muscle injury in antihistamine overdoses and comment on the potential for cross-reactivity of antihistamines with the urine screen for phencyclidine.