Heart failure became a leading cause of mortality in the past few decades with a 
progressively increasing prevalence. Its current therapy is restricted largely 
to the suppression of the sympathetic activity and the renin-angiotensin system 
in combination with diuretics. This restrictive strategy is due to the potential 
long-term adverse effects of inotropic agents despite their effective influence 
on cardiac function when employed for short durations. Positive inotropes 
include inhibitors of the Na+/K+ pump, β-receptor agonists, and 
phosphodiesterase inhibitors. Theoretically, Ca2+ sensitizers may also increase 
cardiac contractility without resulting in Ca2+ overload; nevertheless, their 
mechanism of action is frequently complicated by other pleiotropic effects. 
Recently, a new positive inotropic agent, the myosin activator omecamtiv 
mecarbil, has been developed. Omecamtiv mecarbil binds directly to β-myosin 
heavy chain and enhances cardiac contractility by increasing the number of the 
active force-generating cross-bridges, presumably without major off-target 
effects. This review focuses on recent in vivo and in vitro results obtained 
with omecamtiv mecarbil, and discusses its mechanism of action at a molecular 
level. Based on clinical data, omecamtiv mecarbil is a promising new tool in the 
treatment of systolic heart failure.