Toxic epidermal necrolysis is a rare acute inflammatory multisystem life-threatening condition characterized by widespread epidermal necrosis and profound toxic systemic reaction. Implicated etiologic agents in children include drugs, infections, and autoimmune diseases. The pathophysiology includes separation of the epidermis at the dermal-epidermal junction of both skin and extracutaneous epithelium and mucous membranes. The general consensus is that expeditious transfer to a burn center, maintenance of fluid and electrolyte balance, temperature maintenance, control of evaporative losses, avoidance of use of complicating drugs as corticosteroids and topical sulfa compounds, aggressive septic surveillance, vigorous nutritional support via nasoenteric tube, early ophthalmologic consultation, and appropriate wound care with a regimen of therapy relying on basic principles of treatment of partial-thickness epidermal wounds predict better outcome in the treatment of this disease process. The course of toxic epidermal necrolysis in children, even though dramatic at onset, leads to low mortality when managed appropriately. The current limited published evidence does not clearly delineate differences in epidemiology, pathogenesis, and prognosis of severe skin reactions in children as compared with adults. In this article, we review the available literature on the pathogenesis, clinical features, pathophysiology, treatment, and complications of this rare disease in children.