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Seizures can be a side effect of medications and represent a frequently encountered clinical problem in both acute and long-term settings. They negatively impact quality of life and costs and may affect long-term mortality and morbidity. This paper discusses the pharmacological and pathophysiological mechanisms underlying drug-related seizures, defined by the occurrence of seizures at therapeutic doses, focusing primarily on medications with a direct/mechanistic basis for seizure precipitation. High-risk drugs and populations are discussed, as are diagnostic approaches and management strategies.