Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions that can endanger patient’s life and are therefore considered to be true medical emergencies. Characterized by an abrupt onset of painful, more or less extensive erythematous and erosive lesions of the skin and mucous membranes, SJS and TEN are in fact considered to represent a spectrum of the same disease, differing only in the extent of skin detachment. In addition to the involvement of skin and mucosal surfaces, affection of other organs and potentially fatal complications may develop. These include dehydration, pneumonia and acute respiratory distress syndrome, gastrointestinal ulceration, multiple organ failure and thromboembolic events. Most common causative drugs include allopurinol, antibiotics, anticonvulsants and nonsteroidal anti-inflammatory drugs of the oxicam type. Recently there has been ample evidence supporting the role of genetic background in the development of the disease. Human leukocyte antigen B seems to be the key factor in presenting drugs to T lymphocytes and beginning the immune response which then results in massive apoptosis of epithelial cells. High mortality as well as the risk of longterm sequelae require rapid diagnosis, prompt identification and withdrawal of the culprit drug, evaluation of the prognosis using the SCORTEN (Severity-of-Illness Score for Toxic Epidermal Necrolysis) scale, supportive care and consideration of systemic therapy with immunomodulatory agents.