The current study assessed whether greater use of shift-and persist strategies, which entail the reappraisal of stressors (shifting) and endurance through optimism and meaning-making, buffered the associations between life stressors and adolescents' psychological health (i.e., depressive symptoms, anxiety) and physical health and health behaviors (i.e., self-rated health, sleep quality). Survey data were drawn from a racially/ethnically and socioeconomically diverse sample of 750 9th grade adolescents (53% female). Path analysis revealed racial discrimination, neighborhood risk, and deportation exposure were linked to poorer psychological and physical health, while socioeconomic disadvantage was related to greater anxiety and poorer physical health. Some evidence suggested that shift-and-persist may be protective-reactive, wherein shift-and-persist typically promoted well-being across health domains but more so when the life stressors were at low versus high levels. Shift-and-persist strategies promote both mental and physical health, but the promotive effects appear to be maximized when adolescents' exposure to life stressors is minimal.