The intracellular free Ca2+ concentrations show complex fluctuations in time and space in response to a variety of stimuli, and act as a pluripotent signal for many neuronal functions. Activation of cells is associated with Ca2+ influx from the extracellular space through voltage-dependent and/or receptor-operated Ca2+ channels localized on the plasma membrane, and/or by release of Ca2+ from intracellular stores to reach Ca2+ concentrations of up to micromolar levels. During cell relaxation, calcium concentration decreases to resting levels via ATP-driven Ca2+ transport both to the extracellular space and into the intracellular stores. Thus, Ca2+ homeostasis in neuronal cells is maintained by several systems differing by their mechanisms, biochemical characteristics and intracellular localization. Their biochemical properties and physiological importance as well as cellular localization are discussed in this short review.