Ion channels control electrical excitability in living cells. In mammalian heart, the opposing actions of Na(+) and Ca(2+) ion influx, and K(+) ion efflux, through cardiac ion channels determine the morphology and duration of action potentials in cardiac myocytes, thus controlling the heartbeat. The last decade has seen a leap in our understanding of the molecular genetic origins of inherited cardiac arrhythmia, largely through identification of mutations in cardiac ion channels and the proteins that regulate them. Further, recent advances have shown that 'acquired arrhythmias', which occur more commonly than inherited arrhythmias, arise due to a variety of environmental factors including side effects of therapeutic drugs and often have a significant genetic component. Here, we review the pharmacogenetics of cardiac ion channels-the interplay between genetic and pharmacological factors that underlie human cardiac arrhythmias.