Depression of myocardial contractility plays an important role in the development of heart failure and many inotropic agents were developed to improve the contractile function of the failing heart. Agents that increase cyclic AMP, either by increasing its synthesis or reducing its degradation, exerted dramatic short-term hemodynamic benefits, but these acute effects were not extrapolated into long-term improvement of the clinical outcome of heart failure patients. Administration of these agents to an energy starved failing heart would be expected to increase myocardial energy use and could accelerate disease progression. The role of digitalis in the management of heart failure has been controversial, however, the recent large scale clinical trial has ironically proved that digoxin reduced the rate of hospitalization both overall and for worsening heart failure. More recently, attention was paid to other inotropic agents that have a complex and diversified mechanism. These agents have some phosphodiesterase-inhibitory action but also possess additional effects, including cytokine inhibitors, immunomodulators, or calcium sensitizers. In the Western Societies these agents were again shown to increase mortality of patients with severe heart failure in a dose dependent manner with the long-term administration. However, it may not be the case in the Japanese population in whom mortality is relatively low. Chronic treatment with inotropic agent may be justified in Japanese, as it allows optimal care in the context of relief of symptoms and an improved quality of life. Therefore, each racial group should obtain specific evidence aimed at developing its own guidelines for therapy rather than translating major guidelines developed for other populations.