Emerging evidence indicates that patients with cancer have considerable impairments in cardiorespiratory fitness, which is likely to be a result of the direct toxic effects of anticancer therapy as well as the indirect consequences secondary to therapy (for example, deconditioning). This reduced cardiorespiratory fitness is associated with heightened symptoms, functional dependence, and possibly with an increased risk of cardiovascular morbidity and mortality. Current understanding of the complex interaction between the effects of the tumour and cancer-associated therapies on the organ components that govern cardiorespiratory fitness, and the effects of exercise training on these parameters is limited; further research will be critical for further progress of exercise-based rehabilitation in the oncology setting. We assess the current evidence regarding the level, mechanisms, and clinical importance of diminished cardiorespiratory fitness in patients with cancer. The efficacy and adaptations to exercise training to prevent and/or mitigate dysfunction in conjunction with exercise prescription considerations for clinical use are also discussed.