Like the introduction of digitalis more than 200 years ago, novel medical therapies today have the potential to significantly alter the course of heart failure (HF) and save thousands of lives. This review outlines new directions in HF medical management beyond the foundation of neurohormonal blockade. Furthermore, the role of novel risk factors in HF such as chronic renal insufficiency, anemia, and sleep apnea present tantalizing therapeutic targets to extend the morbidity and mortality benefits of current therapies. The course of time will tell which of these risk factors and therapies can hold promise, given the recent litany of negative trials in the HF arena. Advancements in molecular and genetic techniques have allowed us to begin to consider patient specific therapies and lay the groundwork for even further improvements in treatment of symptomatic HF. Finally, advances in telemedicine and device technology will allow the clinician to remotely monitor useful clinical parameters such as heart rate variability and pulmonary filling pressures to make more informed clinical decision-making and improve outcomes.