© 2015, Springer Science+Business Media New York. REasons for Geographic and Racial Differences in Stroke (REGARDS) is a longitudinal study supported by the National Institutes of Health to determine the disparities in stroke-related mortality across USA. REGARDS has published a body of work designed to understand the disparities in prevalence, awareness, treatment, and control of coronary heart disease (CHD) and its risk factors in a biracial national cohort. REGARDS has focused on racial and geographical disparities in the quality and access to health care, the influence of lack of medical insurance, and has attempted to contrast current guidelines in lipid lowering for secondary prevention in a nationwide cohort. It has described CHD risk from nontraditional risk factors such as chronic kidney disease, atrial fibrillation, and inflammation (i.e., high-sensitivity C-reactive protein) and has also assessed the role of depression, psychosocial, environmental, and lifestyle factors in CHD risk with emphasis on risk factor modification and ideal lifestyle factors. REGARDS has examined the utility of various methodologies, e.g., the process of medical record adjudication, proxy-based cause of death, and use of claim-based algorithms to determine CHD risk. Some valuable insight into less well-studied concepts such as the reliability of current troponin assays to identify “microsize infarcts,” caregiving stress, and CHD, heart failure, and cognitive decline have also emerged. In this review, we discuss some of the most important findings from REGARDS in the context of the existing literature in an effort to identify gaps and directions for further research.