Drug- and toxin-associated seizures (DTS) may result from exposure to a wide variety of agents. Most DTS can be managed with supportive care. First-line anticonvulsant therapy should include benzodiazepines, unless agents require a specific antidote. Phenytoin is generally not expected to be useful for DTS and in some instances may be harmful. In this article the authors discuss the pathophysiology of DTS, the potential differential diagnosis, and the clinical presentation. They also review selected agents that cause DTS and provide an overview of how the clinician should approach the management of patients who have DTS.