A robust literature, over the last years, supports the indication of cardiopulmonary exercise testing (CPET) in patients with cardiovascular diseases. Understanding exercise physiology is a crucial component of the critical evaluation of exercise intolerance. Shortness of breath and exercise limitation is often treated with an improper focus, partly because the pathophysiology is not well understood in the frame of the diagnostic spectrum of each subspecialty. A vital field and research area have been cardiopulmonary exercise test in heart failure with preserved/reduced ejection fraction, evaluation of heart failure patients as candidates for LVAD-Implantation, as well as for LVAD-Explantation and ultimately for heart transplantation. All the CPET variables provide synergistic prognostic discrimination. However, Peak VO2 serves as the most critical parameter for risk stratification and prediction of survival rate.