Estrogens play essential roles in suppressing food intake and preventing body weight gain. Tremendous research efforts have been focused on estrogen physiology in the context of feeding control. Estrogen receptors and the related signals have been attractive targets for development of new obesity therapies. This chapter focuses on the functional interactions between brain estrogens and other appetite-regulatory signals, the critical estrogen receptor isoforms and distinct brain regions that mediate effects of estrogens on feeding, and the intracellular signals that are involved.