Cardiorespiratory fitness (CRF) is inversely associated with the risk for cardiovascular disease (CVD) and clinical events, including death, although most of the available evidence comes from studies performed among older populations. In this issue of JAMA Internal Medicine, the report by Shah et al1 on a large biracial cohort (50% African American) of 4872 young adults followed up for a median of 26.9 years supports the importance of CRF as an independent risk factor for CVD among younger adults. However, the findings suggest that the physiologic mechanism of the significant protective effects of CRF among younger adults (a 15% decrease in total mortality and 12% decrease in first CVD events in 3 decades for each additional minute of treadmill exercise duration at baseline) are related to as yet unclear effects of CRF on myocardial structure and function rather than a direct effect of CRF on atherosclerotic plaque development.