[Author Affiliation]Michael G. Aman. Department of Psychiatry, Ohio State University, Columbus, Ohio.Address correspondence to: Michael G. Aman, PhD, Professor Emeritus of Psychology, The Nisonger Center (OCEDD) Ohio State University, 1581 Dodd Drive, Columbus, Ohio 43210, E-mail: Aman.1@osu.eduFor decades we have known that physical aggression in youth often has dire consequences in later life. The Treatment of Severe Childhood Aggression or TOSCA study was a departure from earlier monotherapy studies of medication treatment for aggression because it entailed an attempt to normalize behavioral outcomes through the use of combined treatment, if needed. The impetus for TOSCA was a series of risperidone studies conducted by Janssen Pharmaceutica and others (e.g., Findling et al., 2000) published in the early 2000s. When designing TOSCA, we were especially interested in risperidone's potential to dampen aggression and other disruptive behaviors. Initially, our focus was comparison of psychostimulant vs. risperidone monotherapy, both with an adjunctive parent training (PT) program. However, using the best data available, power analyses indicated that over 2,000 participants would be needed to have sufficient sensitivity to separate treatments! Eventually, we settled on a combined treatment design not only because it dealt with the statistical-power issue but also because it was ecologically valid (i.e., it followed a common clinical practice; see Farmer et al. 2011 for methodological details).TOSCA is important because it has mapped uncharted territory insofar as pediatric drug research design is concerned. To satisfy the statistical-power issues, we advocated for the complex add-on design (i.e., combined therapy) despite the fact that we, like most practitioners, were trained that simpler is better. The TOSCA design not only called for the use of combined treatments, but one of those treatments was an antipsychotic. Such agents often provoke concern because of their reputation as powerful drugs, because they can cause possible long-term movement disorders, and because of their association with metabolic syndrome. Eventually, the NIMH funded TOSCA and, in so doing, acknowledged the importance of aggression in today's society and the reality that combined pharmacotherapy has become a common practice in child and adolescent psychiatry.The TOSCA participants were 168 children with severe physical aggression (to others, to self, and/or to property) and presence of attention-deficit/hyperactivity disorder (ADHD); psychotic and bipolar disorders were excluded. All study participants received psychostimulant medication and PT in behavior management. If disruptive behavior was not normalized by 3 weeks, then either placebo or risperidone was added as co-therapy from weeks 4 through 9. Psychostimulant+PT+placebo were termed basic treatment, whereas psychostimulant+PT+risperidone were termed augmented treatment. Our earliest reports indicated that augmented treatment was more effective than basic treatment in reducing parent ratings of disruptive behavior (moderate effect size) but not clinician global ratings.Three TOSCA studies appear in this issue. Arnold et al. (2015) examined domains other than disruptive behavior as rated by parents and teachers. They found that augmented treatment resulted in a reduction to teacher-rated anxiety and further that these reductions mediated improvements in parent-rated disruptive behavior. …