Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF in patients older than 65 years. Among elderly women living in the community, HFpEF comprises nearly 90% of incident HF cases. The health and economic impact of HFpEF is at least as great as that of HF with reduced ejection fraction (HFrEF), with similar severity of acute hospitalization rates and substantial mortality. Despite the importance of HFpEF, our understanding of its pathophysiology is incomplete, and optimal treatment remains largely undefined. Unlike the management of HFrEF, there is a paucity of large evidence-based trials demonstrating morbidity and mortality benefit for the treatment of HFpEF. The agents tested in trials to date, which were based upon an incomplete understanding of the pathophysiology of HFpEF, have not been positive. There is an urgent need to understand HFpEF pathophysiology and to focus on developing novel therapeutic targets.