The severity of brain lesions is not a perfect predictor of the severity of cognitive deficits in age-related brain disorders, an observation which has led to the cognitive reserve hypothesis. According to this hypothesis, cognitive reserve modulates the relationship between cerebral lesions and their clinical manifestations by limiting the negative impact of cerebral lesions on cognition. Thus, individuals with high cognitive reserve could sustain a greater amount of neuropathological lesions before they reach the criteria for dementia. The goal of this review is to present and discuss the notion of cognitive reserve, a hypothesis that brings a novel perspective to the complexity of normal and pathological cognitive aging. The present article describes the neuronal mechanisms proposed to underlie cognitive reserve and the factors that increase and decrease reserve. In addition, influent studies that have measured the cognitive reserve hypothesis in clinical populations are presented.