Toxic epidermal necrolysis is an idiosyncratic drug reaction which manifests with extensive epidermal detachment due to the massive keratinocyte apoptosis, mucous membrane involvement, and potentially lethal outcome. It is caused by adverse reactions to drugs, mostly idiosyncratic, unpredictable and independent of the applied dose, which develops 7-21 days after initiation of the drug, and is most commonly caused by the following drugs: sulfonamides, allopurinol, carbamazepine, phenobarbitone, phenytoin and oxycam group of nonsteroidal anti-inflammatory drugs. The treatment outcome depends on several factors, while older age, multiple drug use, late exclusion of the drug inducing toxic epidermal necrolysis, raised serum levels of urea, creatinine and cytopenia are poor prognostic indicators which are rated in SCORTEN scoring which proved to be of great help in the assessment of disease outcome. The basic approach to the treatment is early diagnosis, immediate suspension of the probable inducing drug, and emergency transport to the closest burn center, since treatment in burn units is associated with a lower risk of infection and mortality of these patients. Exclusion of the drug that induced toxic epidermal necrolysis, and supportive therapy, is the first and only therapy for which there is a consensus in different centers. Various forms of adjuvant therapy are also applied: in France, supportive therapy is a standard of care, in Germany it is short-term use of high-dose corticosteroids, while in USA, in the last decade high-dose intravenous immunoglobulins are the most widely accepted treatment modalities. Case reports and small patients’ series described therapeutic effects of plasmapheresis, cyclosporine and other immunosuppressants. In conclusion, elimination of the possible causal agent, rapid transport to the burn unit, and multidisciplinary approach to treatment are of utmost importance for favorable outcome of the disease with 20-30% mortality rate. An update on diagnosis and the treatment of toxic epidermal necrolysis is provided in this review.