Background Agents that increase cardiac contractility (positive inotropes) have beneficial hemodynamic effects in patients with acute and chronic heart failure but have frequently led to increased mortality when given on a long-term basis. Despite this fact, inotropes remain commonly used in the management of heart failure. Methods We reviewed the available data on short- and long-term inotrope use in heart failure, emphasizing high-quality evidence on the basis of randomized trials that were powered to address clinical end points. Results Available data suggest that long-term inotropic therapy has a negative impact on survival in patients with heart failure, regardless of the agent used. The data that inotropic therapy improves quality of life are mixed. High-quality randomized evidence is lacking for the use of inotropes for other heart failure indications, such as for acute decompensations or as a “bridge to transplant.” Conclusions On the basis of the available evidence, the routine use of inotropes as heart failure therapy is not indicated in either the acute or chronic setting. Potentially appropriate uses of inotropes include as temporary treatment of diuretic-refractory acute heart failure decompensations or as a bridge to definitive treatment such as revascularization or cardiac transplantation. Inotropes also may be appropriate as a palliative measure in patients with truly end-stage heart failure. A model of heart failure pathophysiologic features that combines an understanding of both hemodynamic and neurohormonal factors will be required to best develop and evaluate novel treatments for advanced heart failure. (Am Heart J 2001;142:393-401.)