Ischemic Heart Disease, in the absence of obstructive coronary artery disease, is prevalent in women, and constitutes a major risk factor for developing major adverse cardiovascular events, including myocardial infarction, stroke, and heart failure. For decades, diagnosis was considered benign and often minimized; however, it is now known that this etiology caries much risk and is a significant burden to the health care system. This review summarizes the current state-of-knowledge on non-obstructive ischemic heart disease (NOIHD), the association between NOIHD and left ventricular diastolic dysfunction, potential links between NOIHD and the development of heart failure with preserved ejection fraction (HFpEF), and therapeutic options and knowledge gaps for patients living with NOIHD.