The spatiotemporal distribution of cytosolic Ca 2+ ions is a key determinant of neuronal behavior and survival. Distinct sources of Ca 2+ ions including ligand- and voltage-gated Ca 2+ channels contribute to intracellular Ca 2+ homeostasis. Many normal physiological and therapeutic neuronal functions are Ca 2+-dependent, however an excess of cytosolic Ca 2+ or a lack of the appropriate balance between Ca 2+ entry and clearance may destroy cellular integrity and cause cellular death. Therefore, the existence of optimal spatiotemporal patterns of cytosolic Ca 2+ elevations and thus, optimal activation of ligand- and voltage-gated Ca 2+ ion channels are postulated to benefit neuronal function and survival. Alpha7 nicotinic -acetylcholine receptors (nAChRs) are highly permeable to Ca 2+ ions and play an important role in modulation of neurotransmitter release, gene expression and neuroprotection in a variety of neuronal and non-neuronal cells. In this review, the focus is placed on α7 nAChR-mediated currents and Ca 2+ influx and how this source of Ca 2+ entry compares to NMDA receptors in supporting cytosolic Ca 2+ homeostasis, neuronal function and survival.