Publisher Summary Insufficient cardiac output initiates compensatory processes involving increased activity of the adrenergic, renin-angiotensin-aldosterone,, prostaglandin, bradykinin, and vasopressin systems. These compensatory mechanisms further decrease peripheral circulation, leading to congestive heart failure (CHF). Even though progress has been made in understanding this disease and developing new therapies, overall mortality has not declined and many unanswered questions remain. The etiology, pathophysiology, and drug treatment of CHF have been the subject of a number of recent reviews. Clearly, the number and diversity of new agents and mechanisms now available or under development is likely to impact favorably on future therapy for CHF. The increase in survival demonstrated in the V-HeFT study is a milestone and other agents, including angiotensin converting enzyme (ACE) inhibitors, are undergoing similar trials. The potential role of the phosphodiesterase (PDE) inhibitor cardiotonics is likely be defined in the near future following the publication of multicenter trials, involving milrinone and enoximone. As a result of this progress, CHF may be better controlled and overall survival may improve. Nonetheless there remains a challenge to discover drug therapies that not only ameliorate symptoms but have a substantive effect on the disease process and progression.