A systematic review of literature was conducted to examine the association between changes in health-related fitness (e.g., aerobic capacity and muscular strength/endurance) and chronic disease risk factors in overweight and/or obese youth. Studies published from 2000–2010 were included if the physical activity intervention was a randomized controlled trial and reported changes in fitness and health outcomes by direction and significance (p < .05) of the effect. Aerobic capacity improved in 91% and muscular fitness improved in 82% of measures reported. Nearly all studies (32 of 33) reported improvement in at least one fitness test. Changes in outcomes related to adiposity, cardiovascular, musculoskeletal, metabolic, and mental/emotional health improved in 60%, 32%, 53%, 41%, and 33% of comparisons studied, respectively. In conclusion, overweight and obese youth can improve physical fitness across a variety of test measures. When fitness improves, beneficial health effects are observed in some, but not all chronic disease risk factors.