The combination of an increasing number of new cancer cases and improving survival rates has led to a large and rapidly growing population with unique health-care requirements. Exercise has been proposed as a strategy to help address the issues faced by cancer patients. Supported by a growing body of research, major health organizations commonly identify the importance of incorporating exercise in cancer care and advise patients to be physically active. This systematic review comprehensively summarizes the available epidemiologic and randomized controlled trial evidence investigating the role of exercise in the management of cancer. Literature searches focused on determining the potential impact of exercise on 1) cancer mortality and recurrence and 2) adverse effects of cancer and its treatment. A total of 100 studies were reviewed involving thousands of individual patients whose exercise behavior was assessed following the diagnosis of any type of cancer. Compared with patients who performed no/less exercise, patients who exercised following a diagnosis of cancer were observed to have a lower relative risk of cancer mortality and recurrence and experienced fewer/less severe adverse effects. The findings of this review support the view that exercise is an important adjunct therapy in the management of cancer. Implications on cancer care policy and practice are discussed.