There has been intense recent interest in the molecules and pathways governing mammalian body weight regulation. Leptin (OB), an ancestral member of the cytokine family, is an adipocyte-secreted circulating hormone exhibiting weight regulatory properties. Recently, the leptin receptor (OB-R) was identified and shown to exhibit sequence homology and functional similarity to members of the class I cytokine receptor family. The mechanisms governing OB-R triggering and signal transduction have begun to be elucidated, providing new insight into the pathways controlling mammalian body weight homeostasis.