Hypersensitivity to anticonvulsant drugs have been reported many times. But anticonvulsant hypersensitivity syndrome (AHS) is a potentially fatal drug reaction with cutaneous and systemic reaction to the arene oxide-producing anticonvulsants, phenytoin, carbamazepine, and Phenobarbital sodium. The hall-mark features of this syndrome are: Fever, rash and lymphadenopathy. The epoxide hydrolase enzyme may be lacking or mutated in persons in whom AHS develops. The reaction may be genetically determined and familial occurrence of hypersensitivity was observed. The timely recognition of AHS is important, because accurate diagnosis avoids potentially fatal re-exposure and affects subsequent anticonvulsant treatment options. We report two cases of AHS and review the clinical and pathophysiologic features.