Many aspects of calcium homeostasis change with aging. Numerous calcium compartments complicate studies of altered calcium regulation. However, age-related decreases in calcium permeation across membranes and mobilization from organelles may be a common fundamental change. Deficits in ion movements appear to lead to altered coupling of calcium-dependent biochemical and neurophysiological processes and may lead to pathological and behavioral changes. The calcium-associated changes during aging probably do not occur with equal intensity in all cell types or in different parts of the same cell. Thus, cells or compartments with a high proportion of calcium activated processes would be more sensitive to diminished calcium availability. These age-related changes may predispose the brain to the development of age-related neurological disorders. The effects of decreased ion movement may be further aggravated by an age-related decline in other calcium-dependent processes. Depression of some of these calcium-dependent functions appears physiologically significant, since increasing calcium availability ameliorates age-related deficits in neurotransmission and behavior. A better understanding of the interactions between calcium homeostasis and calcium-dependent processes during aging will likely help in the design of more effective therapeutic strategies.