Nutritionists, dietitians and food manufacturers have advocated an increased consumption of whole grain foods. In some countries, this message is supported by governmental guidelines and health claims that can be used on whole grain foods. The bulk of evidence to support these messages comes from observational studies; in some cases, cohort studies with follow-up. Although these data are powerful indicators of the relationship between whole grain intake and improved health, they do not demonstrate causality. Nevertheless, it is difficult to argue against the evidence, particularly for the benefit of whole grains in reducing the risk of cardiovascular diseases. Repeated meta-analyses show that CVD risk is reduced by ≈30% when comparing the lowest whole grain consumers with the highest whole grain consumers. It is argued that to help explain the benefits of whole grain and, in particular, to inform the development of health claims for whole grain foods, intervention studies are needed to link observational data with mechanistic explanations. Until recently, the number of whole grain intervention studies has been very small and most have been conducted in at-risk populations and with small numbers of subjects. Data from larger studies are gradually appearing and, in some cases, the results support the observational data but in others they do not. This report compares observational data with data from intervention studies to reconcile these differences and make recommendations for future research.