Heart failure (HF) is a vicious circle in which an original insult leading to mechanical cardiac dysfunction initiates multiple morphological, biochemical and molecular pathological alterations referred to as cardiac remodelling. Remodelling leads to further deterioration of cardiac function and functional reserve. Interrupting or reversing cardiac remodelling is a major therapeutic goal of HF therapies. The role of molecules and molecular pathways in cardiac remodelling and HF has been extensively studied. Multiple approaches are now used or investigated in HF therapy, including pharmacological therapy, device therapy, gene therapy, cell therapy and biological therapy targeting cytokines and growth factors. This review explores the molecular targets and molecular bases of current and prospective therapies in HF.