Severe cutaneous drug reactions also occur in children and range from reactions with blister forming of skin and mucosa to extensive exanthems with altered differential blood count and involvement of internal organs. The first group includes Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are considered as one disease entity with different degrees of severity and are also referred to as "epidermal" or "epithelial necrolysis" (EN). The group of drug reactions with primarily systemic alterations is represented by a condition known as drug reaction with eosinophilia and systemic symptoms (DRESS).Although EN is generally considered as a drug reaction, a causative agent can only be identified in about 50% of all pediatric cases. Once a clear diagnosis is established, specific treatment measures should be carried out, whereby discontinuation of the causative agent plays a decisive role in drug-induced cases. In order to be able to identify and discontinue the drug responsible, a detailed medication history must be obtained. Certain antiepileptic drugs, sulfonamides and sulfasalazine are among the most frequent triggers of EN and DRESS in children. Supportive therapy including appropriate topical treatment, pain management and ophthalmological consultations are of utmost importance in EN but a short-term immunomodulating treatment with cyclosporine A has been shown to be helpful. In contrast, in DRESS middle to long-term systemic treatment with glucocorticosteroids is recommended.