Abstract The prevalence of dementia and other age-associated cognitive disorders is steadily increasing worldwide. With no cure after diagnosis, successful treatment likely requires maximum adherence to preventative countermeasures. Many potential risk factors are modifiable through exercise. Specifically, mounting evidence suggests that long-term resistance training (RT) can help maintain cognitive abilities with aging and have additional benefits to overall brain health. Physical therapists are uniquely positioned to administer such clinical interventions designed to slow disease progression. However, a neuroscientific foundation for these benefits must be established to justify the integration of RT for brain health into practice. The mechanisms of cognitive decline are commonly linked to fundamental processes of aging. Even healthy older adults experience decreases in physical capacity, vascular function, brain structure and function, glucose regulation, inflammation, mood, and sleep quality. Yet, clinical trials involving RT in older adults have consistently demonstrated improvements in each of these systems with concomitant enhancement of cognitive performance. Beneficial adaptations may indirectly or directly mediate benefits to brain function, and understanding this relationship can help us develop optimal intervention strategies for the aging population.