Drugs that act through noradrenergic and serotonergic mechanisms have historically served as the mainstays of pharmacologic treatments for obesity. This review addresses the following three topics: a brief discussion of older weight loss medications approved for short-term use (benzphetamine, phendimetrazine, diethylpropion, mazindol, and phentermine), as well as over-the-counter adrenergic drugs (phenylpropanolamine and ephedrine); recent clinical studies documenting the safety and efficacy of a new medication for obesity treatment, sibutramine, recently approved by the Food and Drug Administration for long-term use; and recent studies characterizing the valvulopathy associated with fenfluramine and dexfenfluramine, serotonergic medications for obesity which have been removed from the markets.