The cellular distribution of Ca(2+)-binding proteins has been extensively studied during the past decade. These proteins have proved to be useful neuronal markers for a variety of functional brain systems and their circuitries. Their major roles are assumed to be Ca2+ buffering and transport, and regulation of various enzyme systems. Since cellular degeneration is accompanied by impaired Ca2+ homeostasis, a protective role for Ca(2+)-binding proteins in certain neuron populations has been postulated. As massive neuronal degeneration takes place in several brain diseases of humans, such as Alzheimer's disease, Parkinson's disease and epilepsy, changes in the expression of Ca(2+)-binding proteins have therefore been studied during the course of these diseases. Although the data from these studies are inconsistent, the detection and quantification of Ca(2+)-binding proteins and the neuron populations in which they occur may nevertheless be useful to estimate, for example, the location and extent of brain damage in the various neurological disorders. If future studies advance our knowledge about the physiological functions of these proteins, the neuronal systems in which they are expressed may become important therapeutical targets for preventing neuronal death in an array of neurodegenerative diseases.