It is now generally agreed that healthy individuals are characterized by cognitive decline during the later decades of adult life. The acquisition of new information becomes less efficient, which, coupled with a diminished retention of this information for later use, results in substantially poorer memory performance. The ability to plan new activities, solve problems and make complex decisions, as well as cognitive flexibility is noticeably diminished. In addition, attentional processes appear to be invariably poorer in old subjects than in young subjects (for review). While it is quite clearly established that elderly subjects (i.e. after 65 years of age) show a deterioration of cognitive functioning, there is also evidence that this deterioration may start in middle age (40 years). There is large individual variance in age groups; for instance, some old individuals perform on many neurocognitive tests as well as young individuals do. Rowe and Kahn proposed in their influential article to discern between successful aging and usual aging. Successful aging would be due to the effect of chronological age, whereas additional factors would be responsible for usual aging. An important point is the nature of the borderland between usual cognitive aging and pathological conditions such as dementia. Various health-related factors are thought to be important in this respect. They may be a determinant for the transition between successful aging to normal aging and into the borderland with dementia. The Brain & Behavior Research Institute in Maastricht investigates the determinants of successful and pathological aging in a number of related and multidisciplinary projects. This paper describes some major findings of this research programme and gives a theory on the interaction of vulnerability factors and protective factors in their effect on cognitive aging.