Five drugs currently constitute approximately 70% of the world market for antiarrhythmic medications. Since the publication of studies documenting that certain Class I drugs may increase mortality in high-risk postinfarction patients, basic science and clinical studies have focused on Class III antiarrhythmic drugs. However, drugs that prolong repolarization and cardiac refractoriness are sometimes associated with potentially lethal torsades de pointes. Amiodarone, a multichannel blocker, may be the exception to this observation, but it nevertheless fails to reduce total mortality compared with placebo in high-risk patients following myocardial infarction. However, Class III agents remain the focus of drug development efforts because they lack the negative hemodynamic effects, affect both atrial and ventricular tissue, and can be administered as either parenteral or oral preparations. Developers of newer antiarrhythmic agents have focused on identifying antiarrhythmic medications with the following characteristics: appropriate modification of the arrhythmia substrate, suppression of arrhythmia triggers, efficacy in pathologic tissues and states, positive rate dependency, appropriate pharmacokinetics, equally effective oral and parenteral formulations, similar efficacy in arrhythmias and their surrogates, few side effects, positive frequency blocking actions, and cardiac-selective ion channel blockade. New and investigational agents that more closely approach these goals include azimilide, dofetilide, dronedarone, ersentilide, ibutilide, tedisamil, and trecetilide. In the near future, medications will increasingly constitute only part of an antiarrhythmic strategy. Instead of monotherapy, they will often be used in conjunction with an implanted device. Combination therapy offers many potential advantages. Long-term goals of antiarrhythmic therapy include upstream approaches, such as identification of the biochemical intermediaries of the process and, eventually, of molecular and genetic lesions involved in arrhythmogenesis.