Cardiopulmonary exercise testing (CPX) is a well-recognized assessment technique in patients with HF. Ventilatory efficiency, aerobic capacity and heart rate recovery are several parameters obtained from CPX that accurately reflect physiologic function and provide robust prognostic information. Pharmacotherapy is a vital component to the management of patients with HF. Numerous pharmacologic interventions, such as ACE inhibition and beta-blockade have demonstrated significant physiologic and prognostic improvement in this population. Furthermore, a number of investigations demonstrating a positive change in the CPX response resulting from a pharmacologic intervention now exist. Because CPX variables reflect pathophysiologic processes differently, their response to a given pharmacologic is unique. For example, beta-blockade has been shown to significantly improve ventilatory efficiency, one of the most powerful prognostic markers obtained from CPX, while not altering aerobic capacity or heart rate recovery. Conversely, ACE and phosphodiesterase- 5 inhibition appears to improve ventilatory efficiency and aerobic capacity. Given the prognostic value of CPX, gauging its improvement from pharmacotherapy may be advantageous in facilitating optimal titration of medications. A comprehensive review describing the physiologic and prognostic importance of CPX in the context of pharmacotherapy does not exist. This mini review will: 1. Identify key CPX variables obtained from CPX including aerobic capacity, ventilatory efficiency and heart rate recovery, 2. Describe the physiologic and prognostic significance of CPX in the heart failure population, and, 3. Summarize the present body of evidence addressing the change in CPX in response to different pharmacologic interventions including beta-blockade, renin-angiotensin-aldosterone axis inhibition and sildenafil.