Examining American Indian and Alaska Native (AI/AN) resilience using the life course framework could inform public health strategies that support favorable health outcomes, despite adversity (e.g., discrimination, historical loss, comorbidity). A systematic review of peer-reviewed literature published from 1970 to 2015 yielded eight articles on AI/AN life course and resilience. A content analysis identified three themes. AI/AN resilience is 1) an ongoing, dynamic process, 2) evident within linked lives and life transitions, and 3) accessed through cultural knowledge and practice. Resilience research could change the paradigm of AI/AN health research to guide asset-based approaches across the life course.