Acetazolamide (Diamox) is a sulphonamide derivative, which shares with other structurally related agents the ability to inhibit carbonic anhydrase, an effect that is considered to mediate its antiepileptic activity. The efficacy of acetazolamide in patients with epilepsy was reported mainly in the 1950s and only occasional studies were performed several decades later. Acetazolamide shows wide-spectrum anticonvulsant activity in several animal models. It exerts a depressant action in the spinal cord, which is highly selective for the monosynaptic pathway. Induction or inhibition of drug-metabolizing enzymes has no influence on plasma acetazolamide levels. Acetazolamide is a relatively safe drug. Most of the reported side-effects seem to be related to inhibition of carbonic anhydrase, with the exception of idiosyncratic reactions. Acetazolamide is an animal teratogen, and this chapter describes two cases of possible human teratogenicity related to acetazolamide. This should be considered when treating women of childbearing age.