As a key member of the neurotrophin family in the central nervous system, brain-derived neurotrophic factor (BDNF) plays a critical role in the maintenance and plasticity of the nervous system. Its innate neuroprotective advantage can also be shared with the brain when normal aging-dependent processes challenge neural circuits. The intricate relationship between BDNF and resilience during the aging process signifies the molecular mechanisms that underlie the maintenance and protection of brain function, such as cognition, movement and psychological well-being. As BDNF is crucial for neuronal growth and survival, it can also promote resilience against age-related functional decline and frailty, even if it fails to entirely prevent aging-related functional decline. In the present review, we discuss BDNF function from a neuroprotective perspective and how it may promote resilience in aging. We emphasize briefly the principal, well-known cellular hallmarks of brain aging and how BDNF may restrict such disabling molecular dynamics and enhance overall functional resilience in aging. Insight into the molecular pathways through which BDNF reduces age-related brain dysfunctions and/or improves resilience, provides a foundation for developing targeted interventions to promote mental well-being in an aging population.