Obesity has increased at an alarming rate in recent years and is now a worldwide public health problem. In addition to suffering poor health and an increased risk of illnesses such as hypertension and heart disease, obese people are often stigmatized socially. But major advances have now been made in identifying the components of the homeostatic system that regulates body weight, including several of the genes responsible for animal and human obesity. A key element of the physiological system is the hormone leptin, which acts on nerve cells in the brain (and elsewhere) to regulate food intake and body weight. The identification of additional molecules that comprise this homeostatic system will provide further insights into the molecular basis of obesity, and possibilities for new treatments.