The current obesity epidemic and lack of efficient therapeutics demand a clear understanding of the mechanism underlying body weight regulation. The cloning of leptin, a key body weight regulating adipokine released in proportion to the adipose tissue mass, has revolutionized our understanding of the mechanism by which the body weight is controlled. It is now well established that the brain, especially the hypothalamus, maintains body weight homeostasis by effectively adjusting food intake and energy expenditure in response to changes in levels of various nutritional status indicators, including leptin. In addition, one major defect in physiology associated with obesity is reduced fertility. Defects in leptin action result in both obesity and infertility, suggesting that leptin may serve as a link between nutrition supply and reproduction. This review reports recent research advance in neural pathways underlying leptin action on body weight and fertility, and discusses the remaining outstanding challenges.