Alzheimer's disease is a chronic illness characterized by clinical cognitive impairment. A behavioral strategy that is being explored in the prevention of Alzheimer's disease is physical activity. Evidence from randomized controlled trials (RCTs) testing the effects of physical activity for cognitively normal older adults supports that physical activity benefits cognitive performance. Evidence from prospective studies supports a protective effect of physical activity with reductions in the risk of cognitive decline ranging from 28% to 45%. RCTs with cognitively impaired older adults also generally support positive effects with greater benefits evident for aerobic interventions. Research examining the potential moderating role of apolipoprotein E (APOE) has yielded mixed results, but the majority of the studies support that physical activity most benefits those who are at greatest genetic risk of Alzheimer's disease. Future directions for research are considered with an emphasis on the need for additional funding to support this promising area of research.