Many new substances are currently being investigated for their usefulness in the pharmacotherapy of obesity. Most drugs interfere with monoamine neurotransmitter (serotonin, noradrenalin, dopamine and histamine) effects and act as an appetite suppressant. Other approaches are to primarily increase thermogenesis (e.g. β₃-adrenoceptor agonists), or to decrease fat absorption by inhibiting the pancreatic lipase (orlistat). New promising agents are substances that increase the effect of corticotropin releasing factor (CRF) or urocortin in the brain (CRF-binding protein ligand inhibitor) and a neuropeptide Y (NPY) Y₅ receptor antagonist. The clinical relevance of leptin in the therapy of obesity is probably limited, but can not be fully evaluated at the moment. As obesity has a multifactorial basis, all these substances have in common the fact that they can not cure obesity. They should only be used as an adjunct to classical strategies like diet and exercise in severe obesity. For developing new, perhaps even more specific pharmacological agents, further research is needed to understand the individually different genetic and physiological basis of obesity.