It is known for a long time that individuals vary widely in their responses to therapy with different drugs. Variability in drug response may be due to variability in the relationship between drug dose and concentrations of the drug at target sites (pharmacokinetic variability). Another mechanism is that individuals vary in their response to identical exposures to a drug due to variability in the target molecule with which a drug interacts or in biological microenvironment in which the "drug-target" interaction occurs (pharmacodynamic variability). Variants (polymorphisms and mutations) of genes that encode proteins important for pharmacokinetics or for pharmacodynamics are described as important contributors to variable drug actions. In this article pharmacogenetic and pharmacogenomic aspects of antiarrhythmic drug therapy and genetic factors contributing to proarrhythmia are reviewed.