Toxic epidermal necrolysis is a drug-induced, rare, but life-threatening skin eruption. The main differential diagnoses are drug-induced erythema (hypersensitivity syndrome), acute graft-versus-host disease, staphylococcal scalded skin syndrome, and toxic shock syndrome. Because the therapy for toxic epidermal necrolysis and acute graft-versus-host disease differs largely from the others, it is necessary to make an accurate diagnosis. In addition to a detailed medical history, skin biopsy is mandatory because the skin eruptions are not always unequivocal. Discontinuation of the causing agent is crucial, and treatment in specialized intensive care units or burn units is supportive. Currently there is no specific treatment for toxic epidermal necrolysis. Advantages from corticosteroids, plasmapheresis, intravenous immunoglobulin, cyclophosphamide, cyclosporin, andN-acetylcysteine still remain to be established by controlled trials, or have failed to prove a benefit (thalidomide). The patient presented here demonstrates the difficulties in diagnosing toxic epidermal necrolysis in a critically ill patient. A short overview of the pathogenesis and the management of toxic epidermal necrolysis is provided.