Recent progress in genomic sequencing has begun to elucidate the basic mechanisms for several adverse responses, as well as the clinical efficacy, for antiarrhythmic drugs. DNA variants in drug metabolizing enzymes have been implicated in excessive drug accumulation, and genetic variability in drug targets can identify individuals at increased risk for serious side effects, in particular proarrhythmia. It is hoped that future advances in the area of genomic medicine will lead to more individually tailored or personalized pharmacologic therapy in the management of cardiac arrhythmias.