Pediatric obesity continues to be a major public health concern. Once established it is difficult to treat, therefore well-designed and evaluated prevention interventions are vitally important. Schools have an important role in the prevention of childhood obesity, however, their involvement can be limited by a number of constraints and barriers, which need to be considered when designing interventions. Members of the Prevention Stream of the Australasian Child and Adolescent Obesity Research Network have extensive experience in implementing and evaluating school-based obesity prevention initiatives. Based on their collective experience and evidence from implementation research, the aim of this paper was to highlight six areas to consider when designing, implementing and evaluating obesity prevention initiatives in schools. Further, this paper aimed to provide guidance for overcoming some of the challenges and barriers faced in school-based obesity prevention research. The six key areas discussed include: design and analysis; school–community engagement; planning and recruitment; evaluation; implementation; and feedback and sustainability.