OBJECTIVE To systematically review the state of knowledge regarding the understanding and experience of psychological burden and risk of children and adolescents who participate in medical research. Further to provide recommendations to maximize understanding and minimize the burden and risk. METHODS Studies were selected that focus on children and adolescents as source of information via PubMed and PsycINFO; search terms were medical research or trial or experiment, child or adolescent, non-therapeutic, therapeutic, psychology, consent or understanding, risk, burden or stress. RESULTS Of 413 abstracts identified, ten studies on understanding and eight on the experience of burden and risk met our selection criteria. Overall, understanding of the study purpose was reasonable, but low for the procedure. Understanding increased with age and appeared to be overestimated by the young participants. Research on experience of burden was scarce, but identified invasive procedures and procedures related to sexual development as the most burdensome. Only one study assessed psychological risks. CONCLUSION Systematic evidence should be collected on the various aspects of medical procedures related to the experienced burden and risk. This will be useful in informing children and adolescents, parents and medical ethical committees.