Traumatic brain injury (TBI) is a major cause of death and disability in children in both developed and developing nations. Children and adolescents suffer from TBI at a higher rate than the general population; however, research in this population lags behind research in adults. This may be due, in part, to the smaller number of investigators engaged in research with this population and may also be related to changes in safety laws and clinical practice that have altered length of hospital stays, treatment, and access to this population. Specific developmental issues also warrant attention in studies of children, and the ever-changing context of childhood and adolescence may require larger sample sizes than are commonly available to adequately address remaining questions related to TBI. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Pediatric Moderate-Severe TBI (msTBI) group aims to advance research in this area through global collaborative meta-analysis. In this paper we discuss important challenges in pediatric TBI research and opportunities that we believe the ENIGMA Pediatric msTBI group can provide to address them. We conclude with recommendations for future research in this field of study.