Severe skin adverse drug reactions can result in death. Toxic epidermal necrolysis (TEN) has the highest mortality (30-35%); Stevens-Johnson syndrome and transitional forms correspond to the same syndrome, but with less extensive skin detachment and a lower mortality (5-15%). Hypersensitivity syndrome, sometimes called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), has a mortality rate evaluated at about 10%. Drug reactions are self-limited diseases and therefore, generally treatment is symptomatic. Prompt diagnosis, identification of, and early withdrawal of all suspect drugs are the most important preliminaries. The management of the patients must be undertaken in specialized intensive care units, with the same main types of therapy as for burns: warming of the environment, correction of electrolyte disturbances, administration of a high caloric enteral intake, and prevention of sepsis. Efficacy of drugs used in some case reports is difficult to evaluate: intravenous immunoglobulins, cyclosporin, cyclophosphamide, pentoxyfilline, and thalidomide have all been tried. Corticosteroid use is debated and is probably deleterious in late forms of TEN. For DRESS, corticoids are used in cases of life-threatening systemic impairment. Specific nursing care and adequate topical management reduce associated morbidity and allow a more rapid re-epithelialization of skin lesions. After healing, follow-up is needed for ophthalmologic and mucous membrane sequelae. Sunblocks are recommended. Testing for glycemia must be done. Avoidance of the responsible drug and chemically related compounds is essential for the patient and first-degree relatives.