Regulation of coronary blood flow is maintained through a delicate balance of ventriculoarterial and neurohumoral mechanisms. The aortic valve is integral to the functions of these systems, and disease states that compromise aortic valve integrity have the potential to seriously disrupt coronary blood flow. Aortic stenosis (AS) is the most common cause of valvular heart disease requiring medical intervention, and the prevalence and associated socio-economic burden of AS are set to increase with population ageing. Valvular stenosis precipitates a cascade of structural, microcirculatory, and neurohumoral changes, which all lead to impairment of coronary flow reserve and myocardial ischaemia even in the absence of notable coronary stenosis. Coronary physiology can potentially be normalized through interventions that relieve severe AS, but normality is often not immediately achievable and probably requires continued adaptation. Finally, the physiological assessment of coronary artery disease in patients with AS represents an ongoing challenge, as the invasive physiological measures used in current cardiology practice are yet to be validated in this population. This Review discusses the key concepts of coronary pathophysiology in patients with AS through presentation of contemporary basic science and data from animal and human studies.