Despite considerable progress in understanding disease mechanisms and risk factors, improved treatments, and public education efforts, cardiovascular disease (CVD) remains the leading cause of death in the United States. Obesity and physical inactivity, 2 important lifestyle-related risk factors for CVD, are prevalent in the southeastern United States and are becoming more prevalent in all racial groups and areas of the country. In reviewing these risk factors, we explored topics including prevalence and trends in population data; associated psychosocial and environmental factors; and some of the mechanisms through which these risk factors are thought to contribute to CVD. We identified significant, but as yet poorly understood, racial disparities in prevalence of obesity, low levels of physical activity, and correlates of these risk factors and examined important differences in the complex relationship between obesity, diabetes, and cardiovascular disease risk between African American and European American women. The Jackson Heart Study will provide important and unique information relevant to many unanswered questions about obesity, physical inactivity, and obesity in African Americans.