The treatment of patients with congestive heart failure is predicated on an underlying knowledge of the pathophysiology of the syndrome. To date, the most effective therapy has been a combination of diuretics and ACE inhibitors. However, there are specific situations where direct-acting vasodilator therapy is helpful as adjunctive or replacement treatment. As of this writing, digitalis remains the sole orally active positive inotropic drug approved by the FDA for the treatment of patients with heart failure. Although the development of orally active positive inotropic drugs has been generally disappointing, research continues in this area. On the surface, progress in development of vasodilators and inotropic agents for heart failure has been successful, but the average improved survival time is only about 9 to 18 months. Given the current scope of the problem of heart failure, development of newer vasodilators and inotropic therapy as well as agents designed specifically to inhibit the neuroendocrine activation in the syndrome of heart failure can be expected.