The global pandemic of obesity and overweight now affects between 2.8 and 3.5 billion of the world population and shows no signs of abatement. Treatment for what is now recognized as a chronic disease includes pharmacotherapy, considered an essential component of comprehensive therapy. New drug discovery is robust, but the pace of the US Food and Drug Administration approval for obesity drugs has been glacial, and only a handful of approved drugs are available for treating obesity. In the last 20 years, the US Food and Drug Administration has approved 208 drugs for cancer, 118 for cardiovascular diseases, 168 for neurological diseases, and 223 endocrinologic drugs, but only 6 for obesity, 2 of which have been taken off market. Currently, there are only 9 drugs approved by the FDA for obesity treatment. US physicians have turned to off-label drug use in their effort to care for increasing numbers of patients with excess adiposity. Phentermine is the most commonly used drug for treating obesity. Although approved only for short-term use, US physicians have used it successfully for long-term since its initial approval in 1959. This drug, used off-label for long-term, has proven to be safe and effective, far safer than the disease it is used to treat. Phentermine and diethylpropion, an equally safe but somewhat less effective drug, are both generic and therefore inexpensive. These drugs have been maligned inappropriately because their two-dimensional structure diagrams resemble amphetamine and also because of unproven presumptions about their potential adverse effects. In the face of an increasing epidemic, worldwide obese and overweight patients deserve effective treatment that prescribing these drugs could provide, if rehabilitated and used more frequently. US physicians will likely continue to use any drug proven useful off-label for this illness until such time as more effective drugs are approved.