This paper reviews studies that have tested for moderators or mediators of the relation between stressors and child and adolescent psychopathology. Many studies have tested for moderation, but results of research studying moderators have been inconclusive. There have been few theory-based studies and there have been few consistent findings. Far fewer studies have tested for mediation effects, but these studies have generally been theory-driven, have more often built upon one another in an incremental fashion, and have yielded consistent results. In particular, there is substantial evidence for the mediating role of family relationship in the relation between stressors and child and adolescent psychological symptoms. Future studies should integrate moderator and mediator research by testing for specific mediators in relation to particular moderating contexts, so that we can better understand the complex ways in which stressful life experiences affect the well-being of children and adolescents.