<p>The prevalence of HFpEF is rising, especially among older females. Females possess unique attributes in their cardiovascular risk factor profiles, cardiac remodeling patterns, and sex hormonal composition that predispose them to an increased risk of developing HFpEF in comparison to males. Although comorbidities play an important role in driving the cardiac and extracardiac abnormalities manifested in HFpEF, there are ventricular-vascular properties that cannot be explained by comorbidities alone. The “hypertension, arterial stiffness and cardiac remodeling” and “obesity, chronic inflammation and microvascular dysfunction” phenotypic profiles represent two pathophysiological mechanistic pathways that are predominant in the HFpEF syndrome among females. While females exhibit worse symptoms and signs of congestion as well as poorer quality of life, they generally have better clinical outcomes in comparison to males. In this review, we will discuss the available evidence on the sex differences that exist in HFpEF including its pathophysiology, clinical presentation, and outcomes, while concurrently highlighting gaps in the existing literature. We will also mention features of HFpEF that are common to both sexes.</p>