Coronary microvessels play a crucial role for mechanoenergetic interaction between blood flow and myocardial function, which is not uniform transmurally. Thus, highly organized vascular regulations are required for matching local blood flow with myocardial energy requirement. Recently, new technologies to investigate in vivo coronary microcirculation with new knowledge of the signaling molecules for vascular regulation have revolutionized our abilities to understand the integrative regulation of coronary microcirculation. In this review, the mechanical aspects of the interaction between coronary blood flow and myocardium, coronary arte-rial tree and its roles in myocardial blood flow regulation, hierarchical and dynamic control of coronary flow, capillary network and function, function of venous drainage system, and molecular and cellular aspects of integrative coronary blood flow regulation are discussed, focusing on their integrational roles in maintaining coronary microvascular function and cell signaling.