Heart failure (HF) is a complex disease, which involves several physiopathological mechanisms and different genetic polymorphisms. The adrenergic system is directly related to this pathology, as it participates in cardiovascular autoregulation and has a crucial role in the deterioration of cardiac function. The beta-blockers appeared as a great advance in cardiology for the treatment of HF; however, the drug response varies according to each patient, as several factors are associated, such as the genetic one. This review aims at assessing the genetic involvement in the development of HF, the drug response and the prognosis.