Heart failure (HF) is a complex clinical syndrome and a major growing public health problem in Western countries. HF is a leading cause of death and morbidity in modern society, and its incidence continues to increase with the aging population. The complexity of this syndrome and its multifactorial origin constitute problems in the management of patients. Pharmacological treatments aim to interfere with the activation of the neurohormonal and adrenergic systems, which are key pathophysiological mechanisms underlying disease progression. Despite the improvements achieved by current therapies, patients in end stages of the disease still have a poor prognosis. Gene therapy represents a new approach to the treatment of HF, with the ambitious aim of repairing the molecular abnormalities that lead to the disease. Current medical management of clinical HF and novel gene therapies for treatment of HF are presented here.