Fluoxetine is a highly specific serotonin reuptake inhibitor. In studies that used a dose of 60 mg once daily, fluoxetine-treated patients consistently had greater weight loss than placebo-treated patients. In six double-blind, placebo-controlled studies of 6-8 wk duration, mean weight changes on fluoxetine were approximately 0.5 kg/wk. Longer term studies have shown maximum mean weight loss to occur at 12-20 wk of therapy. Studies have consistently shown improvements in indices of glycemic control as well as weight loss in obese diabetic patients. Safety analysis has been performed on data from 3491 obese patients in controlled clinical trials of up to 52 wk duration. Adverse events with an incidence of greater than 5%, which were reported significantly more frequently by fluoxetine-treated patients, were headache, asthenia, nausea, diarrhea, somnolence, insomnia, nervousness, sweating, and tremor. Fluoxetine is effective, well tolerated, and safe in the treatment of obesity and obese diabetics.