Leptin is a pleotropic hormone that acts both centrally and peripherally. Whereas leptin exhibits positive effects on several physiological functions, such as regulation of energy metabolism, reproductive function and immune responses, negative actions, such as enhancement of undesired immune responses in autoimmune diseases, tumorigenesis, elevated blood pressure and cardiovascular pathologies, have also been documented. The recent development of leptin muteins with antagonistic properties and other proteins that block leptin activity opens up new possibilities for their use in research and, eventually, therapy.