Because of the impressive record of ACE inhibitors in patients with heart failure with reduced ejection fraction, the renin-angiotensin-aldosterone system continues to be pursued as a therapeutic target. Furthermore, the optimal treatment of patients with heart failure with preserved ejection fraction remains unclear. Early trials of direct renin inhibitors suggested that they may have a role, but recent results have not been encouraging. Preliminary trials of angiotensin-receptor/neprilysin inhibitors look positive. Whether these or other drugs will alter current recommendations remains to be seen.