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The hypothalamic peptide oxytocin has been increasingly recognized as a hormone and neurotransmitter with important effects on energy intake, metabolism, and body weight and is under investigation as a potential novel therapeutic agent for obesity. The main neurons producing oxytocin and expressing the oxytocin receptor are strategically located in brain areas known to be critically involved in homeostatic energy balance as well as hedonic and motivational aspects of eating behavior. In this chapter, we will review the central and peripheral physiology of oxytocin and the interaction of oxytocin with key hormones and neural circuitries that affect food intake and metabolism. Next, we will synthesize the available data on endogenous oxytocin levels related to caloric intake, body weight, and metabolic status. We will then review the effects of exogenous oxytocin administration on eating behavior, body weight, and metabolism in humans, including in healthy individuals as well as specific populations with suspected perturbations involving oxytocin pathways. Finally, we will address the promise and fundamental challenges of translating this line of research to clinical care.