As the numbers of older adults continue to increase globally, the need for facilitating healthy aging has become critical. While a physically healthy lifestyle, including exercise and diet, is important, recent research has highlighted a major impact of psychosocial determinants of health, such as resilience, wisdom, positive social connections, and mental well-being, on whole health. This article focuses on keeping the mind and brain healthy with psychosocially active aging. It has six sections: Philosophy Concepts of Wisdom, Resilience, and Well-Being; Wisdom: Clinical, Neurobiological, and Evolutionary Perspectives; Resilience, Adaptation, and Augmentation; Psychological Resilience, Brain Health, and Whole Person Health; Preventing Depression and Promoting Resilience and Well-Being in Old Age; and The Centenarian as a Model of Resilience and Well-Being. We discuss the biopsychosocial mechanisms and effectiveness of healthy lifestyle strategies and propose a framework for future research and its practical implications for promoting wisdom, resilience, and well-being at the individual, societal, and policy levels.