This study examined familial factors unique to Latino adolescents within a cognitive vulnerability stress framework, in which negative patterns of thinking contribute to the development of depressive symptoms following stressful life events. Participants were Latino adolescents (N = 90), 12 to 18 years old. Almost half (~48%) reported elevated depressive symptoms. The final regression model explained 67% of the prevalence of depressive symptoms; stressful life events (including family conflict) and a ruminative response style emerged as unique predictors. Additional sociocultural factors contributing to the model’s explanatory power were familism, family cohesion, and perceived discrimination. Rumination and stressful life events should be considered targets for depression prevention and early intervention programs with Latino youth. Such programs would benefit from cultural modifications that encourage family cohesion and a sense of familism.