Anticonvulsant hypersensitivity syndrome (AHS) is a rare, but potentially fatal, adverse reaction that occurs in patients, including children, who are treated with anticonvulsants. During metabolism of the anticonvulsant, toxic arene-oxide compounds are produced. AHS is associated with both cutaneous and systemic symptoms and is associated with multiorgan involvement. Liver damage, in particular, seems to be associated with fatal outcomes. The pathophysiology of AHS is still uncertain but it may be linked to a genetically determined inability to detoxify reactive drug metabolites. The prompt recognition of the first clinical signs of AHS, and the rapid withdrawal of the anticonvulsant, often avoids the progression of symptoms. Pharmacological treatment is essentially based on systemic corticosteroids in association with enteral nutrition, intravenous fluid augmentation, pain relief and ocular care. Intravenous immunoglobulins may also have a possible therapeutic role in some cases. Diagnostic tests, such as patch tests or in vitro assays, for AHS could help to identify patients at risk of developing the syndrome and could represent a first step of primary prevention when applied to relatives of patients.