An increasing number of persons live for nine or more decades and enjoy the benefits of a well-functioning brain until the end of their life. In that respect, the cognitive performance in later life and the quality maintenance of the brain are amazing biological phenomena. Since most nerve cells are generated during pregnancy and have to survive an active lifetime, the brain has to be endowed with a maintenance machinery of surprising long-term quality. During successful, that is, non-pathological, aging in most brain regions, there is very little or no evidence for a decrease in numbers of neurons. In some brain structures, a limited reduction of nerve cells may occur, but it is generally conceived that aging and aging-related cognitive impairments are not the result of massive cell loss but rather the result of synaptic changes, receptor dysfunction or signaling deficits, and metabolic decline. Besides, nerve cell loss during normal aging may be compensated by synaptogenesis, dendritic branching, or in certain brain structures like dentate gyrus by neurogenesis from progenitor stem cells. Yet most human individuals suffer from a mild but life-disturbing condition we call aging-related memory impairment (AMI). In this chapter, some of the mechanisms will be shortly explored that are considered to be causal to non-pathological deterioration of cognitive faculties. In particular, several cellular and molecular neuronal changes will be addressed that occur during aging, the consequences for interneuronal communication and membrane potential, the blood supply to the brain and cerebrovascular condition, and some observations on the protective neuroimmune system of the brain.