Since the 1990s, functional neuroimaging studies on normal and pathological aging showed the involvement of different patterns of activation in comparison with control populations, such as increased frontal activity. These differences have been interpreted as reflecting the implementation of compensatory processes. Confronted to age-related or pathological brain changes, alternative neural networks would be used to perform cognitive tasks. Besides, a rather important variability has been reported in old individuals. This variability concerns not only their cognitive capacities, but also the involvement of different neural pathways according to their performance. This variability could result from differences in cognitive reserve, which can be defined as the capability of an individual to cope with a task in order to optimize his/her performance by the recruitment of different neural networks and/or by using alternative cognitive strategies. The notion of cognitive reserve is very recent and, due to its complexity, is still not well-defined. The main aims of this review are to clarify this notion by summing up the various factors participating in cognitive reserve, to estimate its impact on memory, and to link it with the brain modifications reported in the literature regarding normal aging and Alzheimer's disease. Finally, from a clinical point of view, we suggest to take into account the notion of cognitive reserve during the neuropsychological evaluation of neurodegenerative diseases in the upcoming years.