Far more extensive than the epicardial coronary vasculature that can be visualized angiographically is the coronary microcirculation, which foregoes routine imaging. Probably due to the lack of techniques able to provide tangible evidence of its crucial role, the clinical importance of coronary microvascular dysfunction is not fully appreciated. However, evidence gathered over the last several decades indicates that both functional and structural abnormalities of the coronary microvasculature can lead to myocardial ischaemia, often comparable with that caused by obstructive coronary artery disease. Indeed, a marked increase in coronary microvascular resistance can impair coronary blood flow and trigger angina pectoris, ischaemic ECG shifts, and myocardial perfusion defects, and lead to left ventricular dysfunction in patients who otherwise have patent epicardial coronary arteries. This condition—often referred to as ‘chest pain with normal coronary arteries’ or ‘cardiac syndrome X’—encompasses several pathogenic mechanisms involving the coronary microcirculation. Of importance, coronary microvascular dysfunction can occur in conjunction with several other cardiac disease processes. In this article, we review the pathogenic mechanisms leading to coronary microvascular dysfunction and its diagnostic assessment, as well as the different clinical presentations and prognostic implications of microvascular angina. As such, this review aims to remove at least some of the mystery surrounding the notion of coronary microvascular dysfunction and to show why it represents a true clinical entity.