There are important unmet needs in the treatment of acute heart failure syndromes (AHFS). The unique dual mechanism of action of levosimendan suggests that this new agent may help fill some of these unmet needs. A review of randomized, controlled clinical trials with levosimendan demonstrated that it is well tolerated, and its use results in significantly reduced pulmonary capillary wedge pressure (PCWP) and increased cardiac output. Effects of levosimendan on PCWP and cardiac output are more pronounced than those observed with dobutamine. Levosimendan treatment is also associated with significantly improved clinical symptoms. Moreover, data from 3 trials indicate that levosimendan treatment was associated with improved 6-month survival compared with dobutamine treatment or placebo. Emerging data suggest that levosimendan is beneficial for patients with acute myocardial ischemia. Thus, early clinical indicators suggest that levosimendan may help prevent myocardial injury during hospitalization for AHFS and may be well suited for first-line therapy for AHFS.