A number of maladaptive changes are amplified within the cardiovascular system during the progression of chronic heart failure that makes the decompensation phase difficult to handle. Levosimendan is a new Ca²⁺ sensitizer for the treatment of acutely decompensated heart failure that has proved to be effective during the decompensation of chronic heart failure and acute myocardial infarction. Levosimendan differs from other cardiotonic agents that are used for acute heart failure in that it utilizes a unique dual mechanism of action: Ca²⁺ -sensitization through binding to troponin C in the myocardium, and the opening of ATP-sensitive K⁺ channels in vascular smooth muscle. In general, these mechanisms evoke positive inotropy and vasodilation. Clinical studies suggested long-term benefits on mortality following short-term administration. It may therefore be inferred that levosimendan has additional effects on the cardiovascular system that are responsible for the prolongation of survival. Recently, levosimendan has also been shown to act on mitochondrial ATP-sensitive potassium (mitoK_ATP) channels, an action thought to protect the heart against ischaemia–reperfusion damage. This finding has suggested a possible application for levosimendan in clinical situations in which preconditioning would be beneficial (e.g. in pre- and perioperative settings in cardiac surgery). Collectively, these effects of levosimendan shift the disturbed cardiovascular parameters towards normalization, thereby halting the perpetuation of the vicious cycle of heart failure progression. This may contribute to stabilization of the circulation and improved life expectancy of patients with chronic heart failure.