Patients with heart failure with preserved ejection fraction (HF-PEF) comprise a growing proportion of the overall HF burden. The pathophysiology of HF-PEF is complex, and relates to the interplay between cardiac risk factors (notably diabetes/insulin resistance, hypertension), systemic inflammation, and comorbid medical illness (e.g. chronic kidney disease) that conspire to promote endothelial dysfunction, ventricular-vascular stiffening, and diastolic dysfunction. Efficient diagnosis and optimal therapy remain challenging in this population. Imaging, electrocardiographic, and circulating biomarkers, as well as pharmacogenetics, may help to facilitate HF diagnosis, stratify risk, and individualize therapy. In this review, we focus on established and emerging circulating biomarkers in HF-PE, including circulating biomarkers of myocyte stress, myocyte injury, renal function, systemic inflammation, and fibrosis. Such markers have contributed to better understanding of the pathophysiologic mechanisms relevant to HF-PEF, and may eventually help to facilitate more effective and personalized management of this syndrome.