PURPOSE/OBJECTIVES: To evaluate the effectiveness of exercise interventions on overall health-related quality of life (HRQOL) and its domains among cancer survivors who have completed primary treatment. DATA SOURCES: 11 electronic databases were searched from inception (dates varied) to October 2011. The authors also identified eligible trials through a search of additional sources. DATA SYNTHESIS: 40 trials with 3,694 participants met the inclusion criteria. At 12 weeks, cancer survivors exposed to exercise interventions had greater positive improvement in overall HRQOL (standardized mean difference [SMD] 0.48; 95% confidence interval [CI] [0.16, 0.81]), emotional well-being (SMD 0.33; 95% CI [0.05, 0.61]), and social functioning (SMD 0.45; 95% CI [0.02, 0.87]); and had a significant reduction in anxiety (SMD -0.26; 95% CI [-0.44, -0.07]) and fatigue (SMD -0.82; 95% CI [-1.5, -0.14]). CONCLUSIONS: Exercise programs have a beneficial effect on HRQOL and most of its domains and can be integrated into the management plans for cancer survivors who have completed treatment. Future research is needed to help understand specific attributes of exercise programs that are beneficial for improving HRQOL within and across cancer types. IMPLICATIONS FOR NURSING: Evidence presented in this review supports the inclusion of exercise programs in clinical guidelines for the management of cancer survivors who have completed treatment, such as the Oncology Nursing Society's Putting Evidence Into Practice resource.