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Coronary autoregulation is the intrinsic ability of the coronary circulation to maintain stable blood flow despite fluctuations in myocardial perfusion pressure, provided that metabolic demands remain constant. Central to this process is the dynamic modulation of microvascular resistance within the coronary microcirculation, which acts as the main determinant of coronary blood flow. This regulatory mechanism enables the coronary vasculature to adapt to variations in aortic pressure and epicardial resistance, preserving myocardial perfusion. Historically, the study of coronary autoregulation relied on animal models using implanted flow probes. In humans, modalities such as nuclear imaging and intracoronary Doppler have been employed. Most recently, continuous intracoronary thermodilution has emerged as a robust technique, allowing simultaneous and accurate assessment of absolute coronary blood flow, epicardial resistance, and microvascular resistance. Yet, despite its fundamental role in the understanding of coronary physiology, coronary autoregulation remains complex, often overlooked, and poorly understood. This review focuses on the pivotal role of the coronary microcirculation, specifically microvascular resistance, in maintaining stable resting flow in the context of epicardial coronary artery disease. It provides a theoretical framework, summarizes key animal and human data, and presents an integrative model illustrating the haemodynamic transition from rest to maximal hyperaemia from the perspective of coronary resistance. Finally, it highlights the importance of understanding coronary autoregulation and the interplay between epicardial and microvascular resistance when interpreting not only the clinical presentation of patients with epicardial disease but also the results of the coronary physiological assessment.