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This reprint aims to provide insights into recent knowledge on the cardiovascular system and its adaptation to different diseases and exogenous conditions. Considering the increasing incidence of cardiovascular diseases, a major cause of death worldwide, and the need to attain treatment strategies, knowledge of the physiological processes behind them remains the basis for future research and is a prerequisite for improved clinical studies. Physical exercise is increasingly being regarded as one of the potentially beneficial measures to improve cardiovascular health, interfering with numerous elements of the cardiovascular system and affecting a multitude of potential mechanisms. Its long-term beneficial effects are well known; nevertheless, a lot of questions remain unresolved. Where is the line between benefit and harm? How do different types of exercise affect the cardiovascular system in health and disease, what is the most appropriate measure regarding duration, repetition, and recovery, and if and how can an exercise regime be individually adjusted? In addition, a proper evaluation of physical parameters and cardio-pulmonary and training status is crucial, both in light of a sportsperson's achievements and improvements and from the clinical point of view. In this reprint, scientists from various fields of cardiovascular and/or exercise physiology have presented their new findings, conducting investigations on humans, each importantly contributing to discuss potential controversies and open challenges and questions for future research.