Aging-associated microglial priming results in the potential for an exaggerated neuroinflammatory response to a subsequent inflammatory challenge in regions of the brain known to support learning and memory. This excessive neuroinflammation in the aging brain is known to occur following a variety of peripheral insults, including infection and surgery, where it has been associated with precipitous declines in cognition and memory. As the average lifespan increases worldwide, identifying interventions to prevent and treat aging-associated excessive neuroinflammation and ensuing cognitive impairments is of critical importance. Lifestyle has emerged as a potential non-pharmacological target in this endeavor. Here, we review important and recent preclinical and clinical literature demonstrating the anti-inflammatory effects of lifestyle modifications such as exercise, diet, and environmental enrichment in the context of aging and memory. Importantly, we focus on research indicating that these lifestyle modifications do not need to be lifelong, suggesting that such interventions may be efficacious in the prevention and treatment of aging- and neuroinflammation-associated cognitive impairment, even when initiated in older age.Copyright © 2020 Elsevier Inc. All rights reserved.