The natural alpha-2 antagonist yohimbine promotes sympathetic activity by central as well as peripheral mechanisms, and yet in moderate doses dose not usually raise heart rate, increase blood pressure, or induce anxiety (in contrast to sympathomimetic drugs such as ephedrine). Administered prior to exercise, it boosts lipolysis and serum FFA levels both during and following exercise; blockade of adipocyte alpha-2 adrenoreceptors makes at least a modest contribution to this pro-lipolytic activity. These considerations suggest that pre-exercise administration of yohimbine will lower the respiratory quotient during and following exercise, thus promoting fat loss. Since yohimbine can potentiate postprandial insulin secretion, its bariatric benefits should be greatest if administered on a schedule that minimizes postprandial yohimbine activity. A possible synergism of yohimbine and caffeine should be explored. Pre-exercise yohimbine administration has the potential to down-regulate the lipoprotein lipase activity of visceral adipocytes, increase lipolysis in refractory gynoid fat depots, and improve the impaired lipolytic response to exercise in the elderly.