Physical fitness and activity status are well-documented risk predictors of cardiovascular and total mortality. The purpose of this article is to show how cardiorespiratory fitness predicts atherosclerotic cardiovascular diseases. Measurement of maximum oxygen consumption (VO_2max), defined with or without ventilatory gas analysis during exercise testing, can provide a good estimate for cardiorespiratory fitness, which is an independent marker of the early disease. Low VO_2max has been shown to be comparable with elevated systolic blood pressure, smoking, obesity, and diabetes in importance as a risk factor for mortality, as well as a predictor of coronary artery disease and the progression of atherosclerosis. Cardiorespiratory fitness represents one of the strongest predictors of mortality, emphasizing the importance of exercise testing in everyday clinical practice. In the future, well-defined, disease-specific training programs for exercise prescriptions in different risk groups are needed as a clinical tool.