This chapter addresses pharmacogenetic issues associated with the clinical use of anticonvulsant drugs (ACDs). There are a number of different kinds of natural genetic variation that result in functional protein differences and affect drug responsiveness. The type of variation that is most prevalent in the genome and, arguably, the most relevant to common diseases and complex traits is represented by single nucleotide polymorphisms (SNPs). The chapter presents general comments relevant to the mechanisms of action of conventional classes of ACD. It then addresses how these mechanisms are potentially influenced by genetic variation. Subsequently, commonly used drugs are discussed individually in some depth relative to genes that may affect various aspects of their pharmacology, including metabolism. Among the nonsedating standard ACDs, those most frequently prescribed are phenytoin, carbamazepine, and valproic acid with the depressant drugs phenobarbital and clonazepam also being in common use.