Depression and CHD will become the 2 leading causes of disability in the next decade. Chronic as well as traumatic stress increases CVD risk by about 50%. Although we understand that there are connections between psychosocial stress, affective disorders, and CVD, we do not understand the vast array of brain areas that impact the CV system and the mechanisms connecting them. Neuroscience has made great leaps in understanding the brain in the last 20 years. This more sophisticated understanding of neurobiology needs to be incorporated in our understanding of brain-heart connections. We have a better opportunity with CVD that any other disease to chart brain-body connections and thus promote a whole-body approach to health.