Background: The issue of childhood overweight and obesity has become a global public health crisis. School-based interventions have been developed and implemented to combat this growing concern. The purpose of this review is to compare and contrast U.S. and international school-based obesity prevention interventions and highlight efficacious strategies. Methods: A systematic literature review was conducted utilizing five relevant databases. Inclusion criteria were: (1) primary research; (2) overweight or obesity prevention interventions; (3) school-based; (4) studies published between 1 January 2002 through 31 December 2013; (5) published in the English language; (6) child-based interventions, which could include parents; and (7) studies that reported outcome data. Results: A total of 20 interventions met the inclusion criteria. Ten interventions each were implemented in the U.S. and internationally. International interventions only targeted elementary-aged students, were less likely to target low-income populations, and were less likely to be implemented for two or more years in duration. However, they were more likely to integrate an environmental component when compared to U.S. interventions. Discussion: Interventions implemented in the U.S. and internationally resulted in successful outcomes, including positive changes in student BMI. Yet, varying approaches were used to achieve success, reinforcing the fact that a one-size-fits-all approach is not necessary to impact childhood obesity. However, building on successful interventions, future school-based obesity prevention interventions should integrate culturally specific intervention strategies, aim to incorporate an environmental component, and include parents whenever possible. Consideration should be given to the potential impact of long-term, frequent dosage interventions, and subsequent follow-up should be given attention to determine long-term efficacy. Full article