Major health organizations promote the adoption of a healthy lifestyle, composed of sufficient daily physical activity and a balanced diet for the prevention and management of type 2 diabetes (T2D) and cardiovascular disease risk. In particular, it is recommended that adults accumulate 30 min of moderate-intensity aerobic physical activity on most days of the week. Despite these recommendations, a physically active lifestyle is seldom adopted, and the majority of the North American population remains sedentary. Although the optimal strategy for promoting physical activity in today's environment remains elusive, the evidence for the utility of physical activity in the management of risk factors for T2D and cardiovascular disease is overwhelming. This review examines the influence of aerobic-type physical activity on components of global cardiometabolic risk, that is, the traditional and emerging risk factors for cardiovascular disease and T2D, including visceral obesity, insulin resistance, hypertension, atherogenic dyslipidemia, thrombosis, inflammation, and cardiorespiratory fitness. Where possible, specific consideration is given to the independent effects of an acute bout of physical activity vs. chronic physical activity with weight loss vs. chronic physical activity without weight loss.