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Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of the 64 million people living globally with heart failure and is associated with significant morbidity and mortality. Therapeutic options for HFpEF remain limited, largely due to an incomplete understanding of its complex pathophysiology. A growing body of evidence has highlighted coronary microvascular dysfunction (CMD) as a driver of both the development and progression of HFpEF. CMD is prevalent in up to 75% of HFpEF patients in the absence of obstructive epicardial disease and is associated with increased rates of rehospitalization and mortality. Despite this, CMD is often underdiagnosed in this patient population. A more comprehensive understanding of the link between HFpEF and CMD could provide novel targeted therapeutic strategies. This review aims to elucidate the prognostic significance of CMD in HFpEF, pathophysiologic links between these 2 conditions, and the role of CMD in current and future therapeutic interventions.