Hospitalizations for acute heart failure are associated with high mortality and readmission rates. Ten to 20% of the patients have signs of low cardiac output and fluid overload. The administration of inotropic agents to correct these hemodynamic abnormalities may be indicated in these patients. However, the risk to benefit ratio of inotropic agents is high and an increase of untoward effects and mortality has been suggested by many retrospective analyses and meta-analyses. Limitations of inotropic therapy seem mainly related to their mechanisms of action based, in the case of the traditional agents, on an increase in intracellular cyclic AMP and calcium concentrations. Concomitant peripheral vasodilation, such as in the case of the novel agent levosimendan is another important limitation, above when patients are hypotensive and/or treated with vasodilators and high doses of diuretics. Myosin activators, histaroxime, sarcoplasmic reticulum ATPase activators and metabolic agents seem promising as active through different mechanisms than traditional agents and, in many cases, not associated with tachycardia or hypotension. Further studies are, however, needed.