Intervention research with children and adolescents has suffered from a dearth of relevant theoretical grounding and from the lack of a reciprocal “feedback” mechanism by which clinical trials can inform relevant theorizing and conceptualization. There are hopeful signs, however, of increasing confluence between clinical efforts and theoretical models. Indeed, the key issue I discuss is how intervention studies can yield information about developmental and clinical theory as well as mechanisms related to psychopathology. Specific research examples in the field, particularly those emanating from the Multimodal Treatment Study of Children with attention deficit/hyperactivity disorder (MTA study), reveal that probes of moderator and mediator variables can clearly enhance our knowledge of relevant processes and mechanisms. In fact, recent MTA findings have relevance for models of genetic and epigenetic influence on symptomatology related to attentional deficits and hyperactivity. It would be overzealous, however, to make premature claims regarding etiologic variables from intervention research, as treatment studies typically address variables that are causally far “downstream” from primary causal factors and most clinical trials have statistical power that is barely sufficient for main outcome questions, much less mediational linkages. Overall, the field has severely underutilized experimental intervention research to subserve the dual ends of improving the lives of youth and advancing theoretical conceptualization regarding development and psychopathology.