Despite modern advances in the treatment of the causes and consequences of cardiovascular illness, heart disease and heart failure remain a leading cause of death in the western world. Many novel peptides are emerging as biomarkers and potential therapeutic tools for this debilitating condition. Urocortins represent one such group of peptides whose role in normal cardiovascular physiology and disease states is now increasingly being recognized. The cardiovascular effects of the urocortins are mediated via corticotrophin-releasing hormone (CRH) receptors through a variety of intra-cellular signaling pathways. Studies to date have demonstrated a favourable effect of urocortins on hemodynamic and neurohumoral regulation. They cause relaxation of the vasculature as well as having positive inotropic, chronotropic and lusitropic effects on the heart. This makes the urocortins a potentially attractive target in the treatment of heart failure. Indeed, a number of studies have demonstrated increased urocortin activity in experimental and clinical heart failure, with apparent augmented responses in these states. This article provides a review of the role of urocortins in normal cardiovascular physiology and in the pathophysiology of heart failure.