OBJECTIVE: To determine if cardiovascular exercise programs are beneficial and safe for people with Down syndrome. DATA SOURCES: Electronic databases were searched from the earliest time available through to October 2004 using the following key words: Down syndrome or trisomy 21 in combination with physical fitness, exercise, physical activity, exercise therapy, exercise training, physical training, and aerobic. Additional articles were identified by manual searching and citation tracking. STUDY SELECTION: Two reviewers independently assessed the articles identified in the initial search for the following inclusion criteria: (1) participants with Down syndrome, (2) an exercise program that conformed with the American College of Sports Medicine guidelines for increasing cardiovascular fitness, (3) assessed changes in body structure or function, activity limitation, or societal participation, and (4) used a prospective clinical controlled research design with or without random allocation to groups. Trials of low methodologic quality were excluded (PEDro score, <4). Of the 156 articles initially identified, only 4 met the inclusion criteria and underwent detailed review. DATA EXTRACTION: Data relating to changes in body structure and function, activity limitation, participation restriction, and contextual factors from the included studies were independently extracted by the reviewers on a standardized form. Study quality was assessed using the PEDro scale. DATA SYNTHESIS: Meta-analyses found that cardiovascular exercise programs were effective in increasing peak oxygen consumption (d=.75; 95% confidence interval [CI], 0.34-1.15), peak minute ventilation (d=.71; 95% CI, 0.15-1.28), the maximum workload achieved (d=.96; 95% CI, 0.45-1.45), and the time to exhaustion (d=.72; 95% CI, 0.29-1.15) in people with Down syndrome. No changes were found for body weight (d=.09; 95% CI, -.39 to .57). No adverse effects were reported in any of the studies. CONCLUSIONS: The result of our review support the use of programs designed to improve cardiovascular fitness among people with Down syndrome. However, because only 4 studies were included, the findings need to be interpreted cautiously. High-quality randomized controlled trials should be completed in the future to determine the effect of these programs on activity and social participation.