Half of all heart failure patients have preserved ejection fraction, but there is no established therapy for this patient group. Effective heart failure therapy depends on an understanding of the underlying pathophysiology. This article presents an updated review of knowledge on the causal mechanisms underlying heart failure with preserved ejection fraction (HFpEF).Articles were found by means of a literature search in PubMed. The search combination “heart failure with preserved ejection fraction” OR “HFpEF” OR “diastolic heart failure”) AND (“mechanisms” OR “hypertrophy” OR “inflammation”) yielded 603 hits on 6 April 2017. Relevant articles on causal mechanisms were read in full text.In recent years there has been a paradigm shift with respect to understanding of the pathophysiology of HFpEF. Concentric hypertrophy of the left ventricle with subsequent diastolic dysfunction had long been recognised as an important disease mechanism, but recent research has identified other factors that also contribute to the condition. These include systolic dysfunction, abnormal regulation of heart rhythm, pathological vascular stiffness, autonomic dysfunction and peripheral vasculopathy. Several studies have suggested that comorbidity plays a part by inducing a systemic proinflammatory response which results in multi-organ dysfunction.The pathophysiological picture of HFpEF indicates that the condition resembles a syndrome more than an isolated cardiac disorder. A stronger focus on comorbidity may lead to new diagnostic and therapeutic options.