Over the last decade several pharmacological approaches for acute heart failure have been introduced, however, no drastic change in the medical management apart from device-dependent therapy was observed. Essentially vasodilators and diuretics as primary therapy in acute heart failure was discussed and encouraged in the guidelines but no breakthrough in the treatment of acute heart failure was achieved. More recently, clinical trials of relaxin and its recombinant form, i.e., serelaxin in patients with acute heart failure demonstrated a significant clinical improvement with favorable safety and tolerability profile in symptomatic heart failure patients. This report reviews the potential beneficial effects and role of serelaxin in the setting of acute heart failure.