A number of factors, including physical activity, may contribute to prevention of cognitive decline and delay the onset of dementia. In addition to its convincing multiple benefits, an increasing body of evidence suggests that an active life has a protective effect on brain functioning in elders. Physical activity may also slow down the course of Alzheimer's disease. These hypotheses have led to increasing research in this specific area during the past decade. This review systematically analyzes the current literature on Alzheimer's disease and the effect of physical activity. Epidemiological studies, short-term randomized controlled trials (RCTs) in nondemented participants, and biological research suggest that physical activity improves cognitive function in older subjects. The limitations of these works are discussed. No RCTs have yet demonstrated that regular physical activity prevents dementia. Additional challenging clinical interventional studies are needed to demonstrate this relationship, but accumulating evidence from biological research is available. Defining the optimal preventive and therapeutic strategies in terms of type, duration, and intensity of physical activity remain an open question. In the future, the prevention of Alzheimer's disease may be based on rules governing lifestyle habits such as diet, cognitive activity, and physical activity.