More than 50 years of randomized clinical trials for youth psychotherapies have resulted in moderate effect sizes for treatments targeting the most common mental health problems in children and adolescents (i.e., anxiety, depression, conduct problems, and attention disorders). Despite having psychotherapies that are effective for many children, there has been a dearth of progress in identifying the contextual factors that likely influence who will respond to a given psychotherapy, and under what conditions. The developmental psychopathology evidence base consistently demonstrates that psychosocial risk exposures (e.g., childhood adversities, interpersonal stressors, family dysfunction) significantly influence the onset and course of youth psychopathology. However, the developmental psychopathology framework remains to be well integrated into treatment development and psychotherapy research. We argue that advances in basic developmental psychopathology research carry promising implications for the design and content of youth psychotherapies. Research probing the effects of psychosocial risks on youth development can enrich efforts to identify contextual factors in psychotherapy effectiveness and to personalize treatment. In this article we review empirically supported and hypothesized influences of individual- and family-level risk factors on youth psychotherapy outcomes, and we propose a framework for leveraging developmental psychopathology to strengthen psychotherapies.