This study examines the possibility that relational spirituality may be inversely associated with the relatively higher rates of adolescent depression found in girls as compared with boys. Subjects were 615 adolescents, representing a diverse range of religious, ethnic, and socioeconomic backgrounds. Overall spirituality and depression were measured using The Brief-Multidimensional Measure of Religiosity/Spirituality and the Beck Depression Inventory, respectively. Overall, both level of depression and level of relational spirituality were higher in girls as compared with boys. Regression analyses conducted independently for boys and girls revealed that daily spiritual experiences, forgiveness, and religious coping were associated with less-depressive symptomatology exclusively in girls. This pattern in the findings suggests that uniquely in girls, depression may be associated with disruptions in a relational form of spirituality. © 2007 Wiley Periodicals, Inc. J Clin Psychol 63: 1021–1037, 2007.