Although the cardiac glycosides are universally acknowledged to be important agents in the drug therapy of advanced congestive heart failure (CHF), their role in the treatment of more moderate CHF, particularly in patients in sinus rhythm, remains controversial. Over the past decade, several randomized clinical trials have been undertaken to help clarify the appropriate use of the cardiac glycosides in these patients. Although the data are not conclusive, the available evidence indicates that digoxin is efficacious and relatively safe in patients with CHF whether given alone or in combination with vasodilators. Ongoing myocardial ischemia, hypokalemia and reduced drug clearance due to renal disease or drug interactions remain the clinical parameters most closely associated with digitalis toxicity. However, the recent introduction and widespread availability of a safe and rapidly effective antidote to digitalis preparations--Fab fragments of antidigoxin antibodies--offers the clinician a greater margin of safety in the use of the cardiac glycosides than has been available in the past.