The effects of stress on energy balance and the involvement of the neuropeptide corticotropin releasing factor in modulating the anorexia of stress and sympathetic nervous system tone are well recognized. Currently, studies centered on the roles of the more recently described members of this family of ligands, the urocortins, and their preferred receptor, the corticotropin releasing factor type 2 receptor, suggest that they are important modulators of centrally controlled metabolic functions. In addition, urocortins also regulate fuel utilization in the periphery by acting locally within key metabolic tissues through autocrine and/or paracrine mechanisms. Recent findings have demonstrated that urocortin 2 and urocortin 3, by acting through their specific receptor in peripheral tissues, are novel modulators of glucose homeostasis and metabolic functions.