Recent European Society of Cardiology's (ESC) guidelines on the diagnosis and treatment of acute heart failure (AHF), suggest that an essential target in the management of these patients is to improve symptoms within hours, which should persist until hospital release, also protecting renal function and avoiding ongoing myocardial injury. The vast experience built on the basis of evidence, accumulated regarding the use of levosimendan over the last 10 years, brings with it the possibility of utilizing this drug in multitude of new clinical scenarios. Newly discovered biologic effects of the drug on the failing heart, based on its anti‐inflammatory, anti‐apoptotic and anti‐oxidative properties may explain the clinical efficacy of levosimendan in special sub‐populations of AHF patients. This paper summarizes the current knowledge regarding the use of levosimendan in the early phase of the treatment of AHF, in acute coronary syndromes, its daily use in the critical care environment, perioperatively, and in patients with renal failure.