Severe cutaneous adverse drug reactions are rare, non-predictable, probably of immunological mechanism drug induced reactions, associated to a significant morbidity and mortality and usually leading to hospitalization. Early recognition and withdrawal of the causative drug is mandatory, while providing adequate supportive therapy with systemic immunomodulatory treatments if necessary. Stevens-Johnson syndrome and toxic epidermal necrolysis are severe bullous reactions that differ from each other in the level of skin detachment and are characterized by a great loss of epidermis, mucous membrane involvement and systemic symptoms. Mortality rate is high and surviving patients often suffer from sequelae that impair seriously their quality of life. AGEP is a febrile eruption characterized by numerous small pustules that arise on a widespread edematous erythema. They resolve spontaneously within 1-2 weeks, typically followed by a superficial desquamation. Prognosis is good, usually without any consequences. DRESS is characterized by a prolonged latency period, followed by a variety of clinical manifestations including fever, rash, lymphadenopathy, liver and kidney damage as also other visceral organs involvement. Outcome of the disease varies from the complete recovery to permanent systemic complications. Hepatitis is the most common cause of death. Other severe cutaneous adverse drug reactions include generalized fixed drug eruption, anticoagulant-induced skin necrosis, anaphylaxis and drug-induced erythroderma.