The perception of bicultural stress, stress due to discrimination/prejudice, immigration, and acculturation, was investigated in relation to mental well-being in a sample of urban Latino (n = 304), European American (n = 215), and Asian American (n = 131) 8th grade students. Bicultural stress was reported by all ethnic groups and was significantly associated with more depressive symptoms and less optimism (only for females), after accounting for ethnicity, socioeconomic status, gender, and age. Latino and Asian American youth were more likely to report more stressors, although after controlling for sociodemographic variables the differences predominantly remained only between Asian Americans and European Americans. Lower socioeconomic status, male gender, and not speaking English also were associated with more stress. The negative impact of bicultural stress on adolescent depressive symptoms and optimism indicates the need for mental health researchers and service providers to consider the cultural context of stress for adolescents. (Contains 3 tables.)