With the aging of the population, there is continued emphasis on finding interventions that prevent or delay onset of cognitive disorders of aging. Pharmacological interventions have proven less effective than hoped in this capacity and a greater emphasis has therefore been placed on understanding behavioral interventions that will positively impact dementia risk. Building on a robust animal literature, a substantial volume of research has emerged, particularly over the last 5 years, to suggest that modifiable behaviors impact brain plasticity in both humans and animals. This chapter aims to provide a critical summary of this ever growing body of research, focusing specifically on participation in physical and cognitive activities among older adults and their impact on cognition, the brain, and cognitive aging outcomes. The animal literature on activity and cognition provides a series of hypotheses as to how exercise exerts its cognitive and brain benefits. Research in animals is briefly reviewed in the context of these hypotheses as it provides the groundwork for investigations in humans. The literature on physical and cognitive activity benefits to brain and cognition in humans is reviewed in more detail. The largely positive impact of physical and cognitive activities on cognition and brain health documented in epidemiological, cross sectional, and prospective randomized controlled studies are summarized. While most studies have targeted older adults in general, the implications of exercise and cognitive interventions in individuals with Alzheimer's disease (AD) or mild cognitive impairment (MCI) are also described as is the evidence supporting the ability for physical activity to modify genetic risk. The connection between activity levels and brain volume, white matter integrity, and improved functionality is reviewed. Practical recommendations regarding the nature, duration, intensity and age of onset of physical or mental activity necessary to reap cognitive and brain benefits are also detailed. Most studies have investigated a singular behavioral factor or intervention, but there is some research detailing the impact of combining both mental and physical activity to boost brain health; this emerging literature is also reviewed. Finally, we comment on the limitations of the extant literature and directions for future research, in particular the need for prospective trials of activity interventions in older adults.