Most toxicologic exposures resolve within 24 hours, yet catastrophic outcomes may occur if patients are directly discharged from the emergency department (ED). These cases are, perhaps, the ideal candidates for observation unit (OU) management. This article reviews the criteria for admission and discharge as well as clinical management strategies in the OU for the most common toxicologic exposures. Special attention is given to the multidisciplinary interactions among the ED physician, the medical toxicologist, the physiatrist, and the specialty laboratory.