Healthy lifestyle choices and modern medical advances are extending human lifespan. But longer life is not yet broadly associated with continued mental agility and cognitive awareness. Brain aging and neurodegenerative disease are still barriers to quality of life even though physical longevity continues. Advances in neuroimaging have identified rare individuals that maintain normal brain function despite ongoing Alzheimer’s disease pathology. We propose that these individuals have won a genetic lottery, and that understanding their unique genetic make-up will identify novel ways to promote healthy brain aging for everyone. Our study of rare resilient brains aims to reveal new brain resilience pathways that can be engaged to extend brain health and quality of life that is concordant with physical longevity.