The information presented in this article provides an overview of physiological agents, therapeutics in current use, and medications that have been extensively used in the past but are no longer available, or are not classically considered as anti-obesity drugs. The authors present an extensive review on the criteria for anti-obesity management efficacy, on physiological mechanisms that regulate central and/or peripheral action energetic homeostasis (nutrients, monoamines and peptides), and on beta-phenethylamine pharmacological-derivative agents (fenfluramine, dexfenfluramine, phentermine, diethylpropion, fenproporex and sibutramine), tricyclic derivatives (mazindol), phenylpropanolamine derivatives (ephedrine, phenylpropanolamine), a phenylpropanolamine oxy-tri-fluor-phenyl derivative (fluoxetine), a naftilamine derivative (sertraline) and a lipstatine derivative (orlistat). An analysis of all clinical trials longer than 10 weeks in duration is also presented for medications used in the management of obesity.