Epidemiological studies indicate that between 8 and 20% of children suffer from an anxiety disorder (Costello, Egger, & Angold, 2004). Researchers have worked for many years to map the developmental trajectory of anxiety in children, yet the pathways remain unclear. The primary purpose of this study was to determine the relationship between specific predictors and anxiety in middle school Caucasian and African American adolescents. A secondary purpose was to explore whether acculturation contributes to the prediction of anxiety, after controlling for exposure to negative life events, in the African American adolescents. For the total sample, results indicated that negative life events, social support, coping, and ethnicity were all significant predictors of anxiety, accounting for 18.9% of the variance in anxiety scores. These relationships were confirmed in separate analyses for the African American and Caucasian youth. Furthermore, acculturation moderated the relationship between negative life events and anxiety in the African American sample, as anticipated. More specifically, the relationship between negative life events and anxiety was stronger for those adolescents reporting more affiliation with their own culture. These findings suggest that culture is an important context in understanding the development of anxiety and that it requires additional exploration to understand its relations to the development of mental health problems more broadly.