This literature review is devoted to the use of the antiepileptic drug zonisamide in the initial monotherapy of symptomatic and cryptogenic partial epilepsy. The review is based on the results of the trials, level of evidence A, that demonstrate the efficacy and tolerability of zonisamide comparable to those of carbamazepine. The possible advantages of zonisamide in different clinical situations and characteristics of its use related to molecule structure, pharmacokinetics, mechanisms of drug action are discussed.