Erythema multiforme (EM) is an acute, immune-mediated disorder affecting the skin and/or mucous membranes, including the oral cavity. Target or iris lesions distributed symmetrically on the extremities and trunk characterize the condition. Infections are the most common cause of EM and the most frequently implicated infectious agent causing clinical disease is the herpes simplex virus. The diagnosis of EM is typically based on the patient’s history and clinical findings. Management involves controlling the underlying infection or causative agent, symptom control, and adequate hydration. The epidemiology, pathogenesis, clinical features, diagnosis, and treatment of EM are reviewed in this article.