Resistance exercise training (RET) is gaining broad acceptance as a complement to endurance exercise in the treatment of cardiovascular risk factors. This article reviews the most current and reliable literature regarding the biological mechanisms and potential clinical effectiveness of RET in the treatment of 2 major cardiovascular risk factors, diabetes and obesity, obtained from human subject studies found by querying MEDLINE Plus/Ovid literature search system for the years 1950–2008. RET appears to enhance insulin sensitivity and improve glucose tolerance in a wide range of study groups. In addition, studies have shown that improved glucose uptake is not a mere consequence of the typical increase in fat-free mass associated with RET but is likely a result of qualitative changes in resistance-trained muscle. There is also substantial evidence that regular RET can effectively alter body composition in both men and women. It has been shown to increase total fat-free mass, muscular strength, and resting metabolic rate, and preferentially mobilize the visceral and subcutaneous adipose tissue in the abdominal region. The studies presented in this review demonstrate that RET should remain an important focus of translational research, where clinical trials of RET encourage the performance of mechanistic studies and where mechanistic studies lead to further clinical trials.