Current pharmacological therapy for heart failure (HF) is based on improved understanding of the pathophysiological mechanisms of HF progression. In particular, inhibition of key activated neurohormonal systems (eg, the renin-angiotensin-aldosterone system) and the sympathetic nervous system has been the cornerstone of drug therapy for this condition. However, despite these major advances, many HF patients still only marginally respond to these therapies. Novel therapeutic approaches have been tested. Several recent phase III studies have failed, however, despite intriguing pathophysiological concepts and promising pilot data. In other studies, significant benefits have been observed in certain subgroups only, suggesting the need for a more tailored approach to individual risk and comorbidity. This review will focus on recent and potential future pharmacological HF therapies and where drug treatment may be in the next few years. In discussing future pharmacological therapy for HF, 3 key strategies will be considered: (1) optimization of conventional therapies, (2) a focus on new drug development within areas not yet adequately represented by major clinical data and (3) new drugs affecting novel therapeutic targets. (Circ J 2010; 74: 809 - 817)