Child maltreatment and polymorphisms of the serotonin transporter (5-HTT) and monoamine oxidase A (MAOA) genes were examined in relation to depressive symptomatology. Adolescents (M age = 16.7 years) from low socioeconomic backgrounds with a history of child maltreatment (n = 207) or no such history (n = 132) were interviewed and provided buccal cells for genetic analysis. Gene x environment interactions were observed. Heightened depressive symptoms were found only among extensively maltreated youth with low MAOA activity. Among comparably maltreated youth with high MAOA activity, self-coping strategies related to lower symptoms. Sexual abuse and the 5-HTT short/short genotype predicted higher depression, anxiety, and somatic symptoms. This Gene x Environment interaction was further moderated by MAOA activity level. The results highlight the protective functions of genetic polymorphisms and coping strategies in high risk youth and offer direction for understanding resilience and its promotion from a multiple levels of analysis perspective.