▪ Abstract The normal electrophysiologic behavior of the heart is determined by ordered propagation of excitatory stimuli that result in rapid depolarization and slow repolarization, thereby generating action potentials in individual myocytes. Abnormalities of impulse generation, propagation, or the duration and configuration of individual cardiac action potentials form the basis of disorders of cardiac rhythm, a continuing major public health problem for which available drugs are incompletetly effective and often dangerous. The integrated activity of specific ionic currents generates action potentials, and the genes whose expression results in the molecular components underlying individual ion currents in heart have been cloned. This review discusses these new tools and how their application to the problem of arrhythmias is generating new mechanistic insights to identify patients at risk for this condition and developing improved antiarrhythmic therapies.