The purpose of the present study was to conduct a systematic review of the literature, adhering to PRISMA guidelines, regarding evidence of neuroplasticity in children and adolescents in response to cognitive or sensory-motor interventions. Twenty-eight studies employing seven different types of neuroimaging techniques were included in the review. Findings revealed that significant variability existed across the 28 studies with regard to the clinical populations examined, type of interventions employed, neuroimaging methods, and the type of neuroimaging data included in the studies. Overall, results supported that experience-dependent interventions were associated with neuroplastic changes among children and adolescents in both neurotypical and clinical populations. However, it remains unclear whether these molecular neuroplastic changes, including the degree and direction of those differences, were the direct result of the intervention. Although the findings are encouraging, methodological limitations of the studies limit clinical utility of the results. Future studies are warranted that rigorously define the construct of neuroplasticity, establish consistent protocols across measurement techniques, and have adequate statistical power. Lastly, studies are needed to identify the functional and structural neuroplastic mechanisms that correspond with changes in cognition and behavior in child and adolescent samples.