The majority of studies examining the regulation of coronary blood flow and vascular resistance have considered the coronary circulation as being composed of large conduit vessels and resistance vessels. Recently, it has become apparent that regulation of coronary microvascular resistance is not distributed uniformly, but varies across different segments or microdomains of the vasculature. Generally, small arterioles, those less than 100 microns in diameter, respond differently than larger arterioles and small arteries. There are major differences in the level of autoregulatory control, myogenic control, endothelial modulation and control by metabolic factors across these various microvascular domains. There are also transmural variations which may account for some of the differences in coronary blood observed between epicardial and endocardial regions. In addition, interactions between these various regulatory mechanisms further complicate the understanding of coronary microvascular regulation. Importantly however, it may be these complex interactions and heterogeneous regulatory mechanisms which allow for adequate perfusion of the myocardium under an extreme range of metabolic conditions. This segmental distribution of regulation suggests an integrative hypothesis of regulation whereby a variety of mechanisms play a role in the overall response.