Since their discovery in the brain and gastrointestinal tract nearly 40 years ago, endogenous opioid peptides have been progressively shown to play a role in the regulation of food intake. Animal and human studies regarding opioid peptides and ingestive behavior are reviewed. While the opioid receptor antagonist naltrexone is associated with minimal weight loss as monotherapy, it does have potential utility in the treatment of obesity when combined with the pro-opiomelanocortin activator bupropion.