Disabling chronic pain is a common experience for children and adolescents. However, the evidence base for chronic pain interventions for youth is extremely limited, which has hindered the development of evidence-based practice guidelines for most pediatric chronic pain conditions. To review and provide recommendations on clinical trial design and evaluation in children and adolescents with chronic pain. In this article, we summarize key issues and provide recommendations for addressing them in clinical trials of chronic pain interventions in children and adolescents and their families. To stimulate high-quality trials of pediatric chronic pain management interventions, attention to key issues including sample characterization, trial design and treatment administration, outcome measurement, and the ethics of intervening with children and adolescents, as opposed to adults with chronic pain, is needed. Future research to develop interventions to reduce or prevent childhood chronic pain is an important priority area, and requires special considerations in implementation and evaluation in clinical trials.