The underlying proposition for any experimental/therapeutic trial is the uncertainty that the risks of treatment will be outweighed by its benefits. For some therapeutic interventions (e.g., exercise programs, vitamin supplementation), the potential for treatment-emergent adverse events may prima facie be low or negligible, whereas for others (e.g., chemotherapy, invasive surgeries), the potential for treatment-emergent adverse events may be substantial. Because it is both scientifically and ethically necessary to determine efficacy, tolerability, and safety of medical treatments, a number of strategies have been developed to increase the probability that evidence of both effect and harm can be reasonably identified before the intervention passes into general use. One of those strategies is the randomized, placebo-controlled trial (RCT) in the pharmacotherapy of child and adolescent psychiatric disorders. In addition, a variety of structures and procedures have been developed to mitigate the risk to subjects who agree to participate in therapeutic research. These safeguards include but are not limited to study approval from independent institutional review boards, informed consent, and independent third-party audit of data and procedures. One of the structures that has been developed to improve research subject safety in therapeutic research in which risks for harm may either be high or unknown is that of the Data Safety and Monitoring Board (DSMB). DSMBs were introduced into medical therapeutics research in the 1990s and have become increasingly important in monitoring the safety of subjects participating in clinical trials. Although they have been relatively well established in some medical disciplines such as cancer or HIV/AIDS research, they have generally not been applied to psychopharmacological research in young people. The authors of this article argue that they should.