Complex ventricular premature depolarizations (VPDs) in the presence of ischemic heart disease, especially in the presence of left ventricular dysfunction, are associated with an increased incidence of sudden cardiac death. However, we have no hard data from prospective, randomized, double-blind studies demonstrating that abolition or reduction of VPDs will reduce mortality. Moreover, the drugs available to treat VPDs may not abolish or reduce VPDs in the individual patient, occasionally may exacerbate ventricular arrhythmias, and may produce toxic effects. Spontaneous variability of VPDs may also mimic an antiarrhythmic drug effect. Clinical judgment must be used to determine which patients with VPDs should be treated, with which antiarrhythmic drug or combination of drugs, given in what doses, to which blood levels or therapeutic endpoints. We need to determine in the individual patient which methods of monitoring the efficacy and toxicity of antiarrhythmic drugs should be used and how often. I treat patients with known heart disease with chronic oral antiarrhythmic drugs if they have frequent VPDs (more than five per minute), multifocal VPDs, couplets or short runs of ventricular tachycardia, or the R on T phenomenon. Patients with complex VPDs should especially be treated with antiarrhythmic drugs if they have survived a cardiac arrest, if they have poor left ventricular function, if they have sustained an acute myocardial infarction within 1 year, if they have unstable angina pectoris, if they have severe stable angina pectoris, if they have exhibited complex VPDs during treadmill stress testing associated with a low heart rate, an inappropriate blood pressure response to exercise, S-T segment depression at least 2.0 mm, or a short exercise duration, if they have a prolonged Q-Tc interval, and if they are symptomatic. I do not treat VPDs in asymptomatic patients who have no evidence of heart disease.