In this article we present evolutionary aspects of the dual role of Ca2+ as signaling molecules and cytotoxic cations. We discuss the mechanisms of calcium homeostasis in neurons, taking into account the specific features of excitable cells and the mechanisms of generation and transduction of calcium signals. Based on this information we outline the role of Ca2+ ions in specific functions of the nerve cell, such as excitability, propagation of the action potential, synaptic transmission, neuronal plasticity and various forms of mobility. Then we discuss the role of disturbances of calcium homeostasis and signaling function in the mechanisms of injury and death of neurons in acute diseases with special regard to cerebral ischemia, and in chronic neurodegenerative disorders.