Obesity is a significant health problem worldwide and is associated with a 
number of co-morbidities including type 2 diabetes mellitus, hypertension, 
dyslipidemia, obstructive sleep apnea, and cardiovascular disease. A number of 
different pathophysiologic mechanisms including increased inflammation, 
oxidative stress, and insulin resistance have been associated with initiation 
and progression of atherosclerotic disease in obese individuals. Lifestyle 
modifications have provided modest results in weight reduction and the focus of 
interest has now shifted towards drug development to treat severely obese 
individuals with a body mass index (BMI) >30 kg/m(2) or those with a BMI >27 
kg/m(2) who have additional co-morbidities. Different regimens focusing on 
dietary absorption or acting centrally to control hunger and food intake have 
been developed. However, their weight loss effect is, in most cases, modest and 
this effect is lost once the medication is discontinued. In addition, long-term 
use of these drugs is limited by significant side effects and lack of long-term 
safety and efficacy data. Orlistat is the only US FDA-approved medication for 
long-term use. A number of new medications are currently under investigation in 
phase III trials with promising preliminary results. This review comments on 
available anti-obesity pharmacologic regimens, their weight-loss benefit, and 
their impact on cardiovascular risk factors.