Pharmacological therapies remain the primary strategy for treating patients with acute and chronic heart failure. Several novel neurohormonal antagonists, inotropic agents, immune modulators, and metabolic and replacement therapies are currently in development to meet the demands of an increasing number of patients with heart failure. The success in drug development in this field will require a better understanding of the effects of heart failure on drug dosing, better integration of novel and existing drug therapies, the development of more reliable surrogate markers to effectively tailor medical therapy to individual needs and the ability to detect and treat patients at risk before the onset of heart failure.