Atherosclerosis remains the underlying cause of cardiovascular disease and is a dynamic process involving inflammation, haemostasis, endothelial dysfunction, and angiogenesis. Studies of circulating factors from peripheral blood can provide an insight into this pathophysiology but may remain indicative of a more generalized, systemic process. More localized interaction(s) within the heart may be better studied from coronary blood samples. Indeed, an increasing number of prospective studies show good correlation between indices of these processes and clinical outcomes. As local sampling offers a unique way of assessing the local cardiac milieu, this may prove useful in the monitoring of both local/systemic drug therapies and interventional technologies.