Urine drug testing is now mandatory in many industries. We report the first case, to our knowledge, of an adverse consequence of drug testing in the workplace: acute water intoxication. We discuss normal water metabolism and the adverse effects of water loading and impaired renal function on free water clearance. We present a literature review of seven other cases of acute voluntary water intoxication in patients without chronic psychiatric or neurologic illness. For workers undergoing urine drug testing we conclude that risk factors for acute water intoxication include (1) intake of more than 1 L of water and (2) impaired urine dilution. In a recently drug-tested worker, symptoms of cerebral dysfunction should suggest the possibility of water intoxication.