After more than two centuries of administration of digitalis glycosides to patients with cardiac disease, empirical observation and tradition remain the basis for much of the clinical application of these drugs. Many questions remain, and the role of digitalis in the management of congestive heart failure and cardiac rhythm disturbances is changing with improvement in our understanding of the pathophysiology of these conditions and the availability of newer effective agents that may have less potential to cause life-threatening toxicity. Nevertheless, digitalis glycoside therapy is a familiar therapeutic intervention for the majority of physicians and remains appropriate in carefully selected patients. The development of digoxin-specific Fab fragments has led to improvement in treatment of advanced and refractory digitalis toxicity and opens up the possibility of improvement in diagnosis of less clinically obvious cases of digitalis intoxication. The role of digitalis glycosides in the management of supraventricular tachyarrhythmias and congestive heart failure in the presence of sinus rhythm should now be revised. In each of these clinical circumstances, alternative drugs or other modes of therapy have been developed that reduce the dependence of clinicians on digitalis as the sole or primary approach to management. In the immediate management of paroxysmal reentrant supraventricular tachyarrhythmias, verapamil has largely replaced digoxin as the drug of choice, although digoxin has an ancillary role, especially in patients with impaired ventricular function. In the management of patients with atrial fibrillation or atrial flutter with a rapid ventricular response, verapamil or diltiazem and beta-adrenergic-blocking drugs will effectively slow the ventricular response, thus reducing the likelihood of approaching the threshold of digitalis toxicity to achieve adequate rate control. In the treatment of patients with congestive heart failure and normal sinus rhythm, one must now recognize a subset of patients with diastolic rather than systolic dysfunction who are best treated by correcting underlying causes of left ventricular hypertrophy or ischemia rather than inotropic support with cardiac glycosides. Symptomatic patients with dilated ventricles and impaired contractile function should undergo correction of abnormalities of preload with vasodilators acting on the venous bed as well as diuretics, and reduction of elevated afterload with vasodilators that reduce arteriolar resistance and thus improve ventricular emptying.(ABSTRACT TRUNCATED AT 400 WORDS)