Chronic heart failure represents a fundamental health and financial challenge for Flanders and European society. While physical exercise represents a key rehabilitation strategy, up to 50% of patients have been characterized as nonresponders by previous studies for reasons that are still unclear. In this context, research focused for a long time on the central limitations (the heart) as the cause of exercise intolerance in these patients, but it has been recently proposed that limitations acting within the working muscles may also play a primary role. This would suggest a possible new target to improve rehabilitation based on patients’ main limitations (central vs peripheral). Still, the lack of knowledge on the primary factors inducing exercise intolerance in these patients, calls first for further investigation. With a strong interdisciplinary and multicentric nature, this project aims at: i) obtaining insight into the causes of exercise intolerance in chronic heart failure; ii) evaluating the effectiveness of the current rehabilitation and identifying the characteristics of nonresponders to exercise; iii) testing the efficacy of a tailored rehabilitation approach based on patients’ main limitations. The final outcome will be a better understanding of the disease and an innovative rehabilitation paradigm to improve its nonpharmacological management. This will have crucial importance as the incidence of heart failure is predicted to increase strongly in the next ten years.