Alzheimer's disease (AD), as a neurodegenerative process caused by widespread senile plaques and neurofibrillary tangles, is faced with an increasingly higher incidence as the global aging develops. Cognitive reserve (CR) hypothesis is proposed to elucidate the disjunction between cognitive performance and the pathological level of AD, positing that some life span experiences will lend protection from AD pathological insults. We provide an overview on recent studies involved in validation of the hypothesis as well as the association between AD and CR proxies, such as educational attainment and quality, occupational activity, leisure activity, general intelligence, and enriched environment. We further discuss some potential mechanisms by which CR proxy acts against AD pathological insults including neuroplasticity, neurogenesis, and locus coeruleus-noradrenergic (LC/NA) system. Finally, we review the applications of CR theory for AD prevention and therapy, particularly through physical activity and cognitive training strategy. We believe that a better knowledge of the relationship between AD and CR, accompanied by a successful transition of research accomplishments into practice, will impart much relief to individuals suffering from AD.