In industrial nations the most common form of malnutrition is obesity. Obes
ity is a chronic disease associated with increased morbidity and mortality.
Unfortunately, the simplest treatment for obesity, increasing physical act
ivity and reducing caloric intake, for the vast majority of patients is com
pletely ineffective over the long term. Weight lost is quickly regained, an
d body weights after intervention often exceed pretreatment levels. Early p
harmacotherapy had been successful in reduction and maintenance of weight l
oss; unfortunately, unforeseen side effects contributed to an unacceptable
risk/benefit balance that necessitated the withdrawal of many of these agen
ts. Current pharmacotherapy is limited, with only 2 compounds accepted for
long-term use for the treatment of obesity. Both sibutramine and orlistat c
ontribute to modest weight loss and maintenance and reduce obesity-associat
ed risk factors. Beginning with the discovery of leptin in the mid-1990s, a
renaissance in obesity research has taken place. This research has provide
d more detailed insights into the regulation of energy homeostasis. The cen
tral feedback regulation loops involving the leptin and melanocortinergic p
athways have provided several targets for therapeutic intervention, includi
ng leptin analogs and melanocortin agonists. Several peripheral targets inc
luding uncoupling proteins and beta (3)-adrenergic receptor are also being
explored for their anti-obesity potential. Therefore, it can be expected th
at new pharmacotherapies will be available to help combat the epidemic of o
besity.