Acute heart failure (AHF) represents a major healthcare burden with a high risk of in-hospital and post-discharge mortality, which remained almost unchanged in the last few decades, underscoring the need of new treatments. Relaxin is a naturally occurring human peptide initially identified as a reproductive hormone and has been shown to play a key role in the maternal hemodynamic and renal adjustments that accommodate pregnancy. Recently, the new molecule serelaxin, a recombinant form of the naturally occurring hormone relaxin has been studied in patients hospitalized for AHF. In addition to vasodilation, serelaxin has anti-oxidative, anti-inflammatory and connective tissue regulating properties. In preclinical studies, it reduced both systemic and renal vascular resistance and, in the clinical trials Pre-RELAX-AHF and RELAX-AHF, it improved dyspnea and signs of congestion. In addition, serelaxin was associated with a reduction of 180-day mortality. The aim of this review is to summarize the pharmacological properties of serelaxin and the results of the preclinical and clinical studies.