Over the last few years the development of calcium-sensitizing agents has led to a new approach to the treatment of congestive heart failure (CHF). These novel inotropic agents act directly on the contractile protein systems and correct the reduced responsiveness of the myofilaments to calcium. The resultant favorable inotropic activity of this new class of cardiotonic agents may represent an important pharmacologic approach to the future treatment of acute and chronic CHF. This brief review summarizes the cardiotonic effects of calcium sensitizers, with particular emphasis on the hemodynamic actions of these drugs in various in vitro and in vivo heart preparations. We also attempt to draw conclusions for the therapeutic exploitation of these agents and delineate their possible role in the therapy of CHF.