Severe cutaneous adverse reactions are associated with significant morbidity and mortality. They may be life-threatening for the affected patient and difficult to treat. Such conditions include toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalized exanthematous pustulosis and drug reaction with eosinophilia and systemic symptoms. Due to the fact that prognosis, etiology and treatment of the various reactions differ, a clear diagnosis based on the specific clinical pattern is important. This review will focus on the clinical presentations, pathogenesis, and important diagnostic and therapeutic considerations in the management of SJS and TEN.