Research involving children is necessary to bridge the gap created by years of applying the findings of adult clinical trials to children. Given the mandate from the National Institutes of Health to include children in clinical trials, pediatric nurses will undoubtedly be asked to assist with pediatric research projects. Nurses working with children must consider the unique legal and ethical issues surrounding children as study participants. The purpose of this article is to examine issues related to children participating in clinical research. A review of pertinent literature is summarized, and practical approaches to the recommendations are discussed.