Conducting clinical trials in pediatric critical care patients are necessary both to determine the value of new treatment strategies and to improve clinical outcomes. However, there are significant challenges to clinicians, parents, and child subjects. There is a serious danger to children through exposure to unforeseen risk as a result of lack of pediatric trials if "trickle down" from adult treatments is permitted. The relatively small size of the pediatric critical care population and relatively low mortality rates limit the utility of mortality as a primary trial outcome in many trials. Innovative trial designs including incorporation of nonfatal outcome measures are increasingly being developed. Increasingly, effective research collaborations are developing either for specific clinical trials or to form the base from which clinical trials are commissioned and supervised. Involvement of children and parents in the development of clinical trials is recommended and valued both by ethical review boards and patient/parent support organizations.