Background:Heart failure is a prevalent condition of major public health importance that leads to significant morbidity and mortality despite the use of current evidence-based therapy. Further development of novel therapies to alleviate symptoms, improve functional status and ultimately clinical outcomes are needed. Cardiac function alone cannot explain all aspects of the heart failure syndrome: hence a search for peripheral mechanisms and inter-connected cardiac and non-cardiac pathways has ensued. Testosterone plays an integral role in multiple organ systems for growth, development and maintenance of health with known effects on peripheral musculature, vasculature, sympathetic tone, endothelial function and restoration of muscle metabolic function which would be beneficial in HF. Chronic HF has been associated with reduced testosterone levels, and low testosterone levels have been linked to reduced VO2, increased BNP and ANP levels, and worse clinical outcomes. Testosterone supplementation acts as a peripheral vasodilator and acutely increases cardiac output,which would improve oxygen delivery to skeletal muscles and secondarily delay transfer to anaerobic metabolism and depletion of high-energy phosphates. The increase in muscle mass associated with testosterone therapy may also result in increased endurance and decreased muscle fatigability in HF patients. Early small trials demonstrate safety, tolerability and an improvement in exercise walking distance in patients with HF. We contend that the time is now ripe for an adequately-powered phase II trial in order to test if this therapy can improve symptoms and functional status for patients with heart failure.