The hormone leptin is secreted by adipose tissue in proportion to fat mass to signal the repletion of body energy stores to the neuroendocrine system. Leptin acts on neurons in the hypothalamus and elsewhere in the brain to decrease appetite and regulate the activity of the thyroid, adrenal, growth, gonadal, and lactational axes. Conversely, absence of leptin signaling initiates the neuroendocrine starvation response. Leptin mediates these effects by activating the long form (LRb) of its receptor. One LRb signal, STAT3, has recently been shown to play a critical role in the regulation of body weight and some elements of neuroendocrine function (thyroid, adrenal, lactation), although the participation of STAT3 in the gonadal and growth axes is negligible. We discuss these findings in the context of the hypothalamic neuroendocrine system as it is presently understood.