Phenytoin is one of the antiepileptic drugs most widely prescribed. This drug has narrow therapeutic index, and often treated for a long time. Phenytoin was metabolized by CYP2C9 (major) and CYP2C19 (minor). The purpose of this review is to give a comprehensive understanding of the influence of genetic polymorphisms toward phenytoin response. The methods of review were searching through Pubmed with keywords pharmacogenetic, phenytoin and epileptic. We found 41 journals but only 19 met the criteria, namely: a. human subjects, b. discuss the impact of genetic responses phenytoin. The author adds 1 journal, 1 web (drug bank) and books so that became 22. Search results conclude that: the polymorphisms of genes of metabolizing enzyme (CYP) affect to the kinetic profile of phenytoin.