Although progress has been made to understand the association between physiological and lifestyle behaviors with regard to obesity, ethnic differences in markers of obesity and pathways towards obesity remain somewhat unexplained. However, obesity remains a serious growing concern. This paper highlights ethnic differences in African Americans and Caucasians that may contribute to the higher prevalence of obesity among African Americans. Understanding ethnic differences in metabolic syndrome criteria, functioning of the hypothalamic pituitary adrenal axis, variations in glucocorticoid sensitivity and insulin resistance, and physical activity and cardiovascular fitness levels may help to inform practical clinical and public health interventions and reduce obesity disparities.