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This study systematically reviewed the impact of physical exercise interventions on physical fitness for individuals with Down syndrome. Articles published in English were searched from five major electronic databases, namely, CINAHL, Medline, PsychINFO, SPORTDiscus, and PEDro from inception until April 2013. These studies were screened through predefined inclusion and exclusion criteria. Data were then extracted and synthesized from the studies included. Meta-analyses were carried out where appropriate. Ten studies fulfilled the inclusion criteria. Of the 10 studies, five studies were found to have high quality research methodology according to the PEDro scale. Varying exercise programs were used and four different fitness outcomes were evaluated: (i) balance, (ii) muscle strength and endurance, (iii) cardiovascular fitness, and (iv) body composition. Exercise interventions led to moderate to high effects on improving muscular strength and balance (=0.74–1.10) whereas other outcomes showed less conclusive or limited positive evidence. Trends in the results suggest that exercise interventions improve muscular strength and balance. Suggestions for future research include follow-ups to the intervention to examine the longitudinal effects of exercise as well as controlling for confounding factors such as participants’ compliance rate and severity levels of Down syndrome to enhance the effectiveness of the interventions.