Erythema multiforme (EM) is a rare acute mucocutaneous condition caused by a hypersensitivity reaction with the appearance of cytotoxic T lymphocytes in the epithelium that induce apoptosis in keratinocytes, which leads to satellite cell necrosis. EM can be triggered by a range of factors, but the best documented association is with preceding infection with herpes simplex virus (HSV). Most other cases are initiated by drugs. EM has been classified into a number of variants, mainly minor and major forms, as it may involve the mouth alone, or present as a skin eruption with or without oral or other lesions of the mucous membrane. EM minor typically affects only one mucosa, and may be associated with symmetrical target skin lesions on the extremities. EM major typically involves two or more mucous membranes with more variable skin involvement. A severe variant of EM major is Stevens-Johnson syndrome, which typically extensively involves the skin. Both EM major and Stevens-Johnson syndrome can involve internal organs and produce systemic symptoms. Treatment of EM is controversial, as there is no reliable evidence. Precipitants should be avoided or treated and, in severe cases, corticosteroids may be needed. Toxic epidermal necrolysis may be similar to Stevens-Johnson syndrome, but many experts regard it as a discrete disease, and therefore it is not discussed here.