There is much evidence that contractility is depressed in failing heart. However, the use of interventions that arguments the contractile force by increasing an intracellular free Ca²⁺ ion has not been a success in treatment with chronic heart failure. Unfortunately these drugs are associated with an increased risk of mortality. New inotropic agents (pimobendan, levosimendan, MCI-154, EMD57033 and CGP48506) have been developed that increase the responsiveness of contractile proteins to Ca²⁺ These drugs can exert force of contraction without inducing arrhythmia and increasing energy consumption by Ca²⁺ overload. Therefore these classes of drugs are defined as Ca²⁺ sensitizers and are expected as a possible pharmacotherapy for chronic heart failure. The Ca²⁺ sensitizers divide into three classes dependent of their mode of action. The present article reviews the molecular mechanisms of action of Ca²⁺ sensitizers.