Epithelia, like other vertebrate cells, are equipped with an extensive network of signaling pathways, involved in the regulation of a large variety of distinct cellular functions. Amongst many the intracellular Ca2+ [Ca2+]i signal is the most common one. On the one hand, [Ca2+]i is involved in regulation functions of general cell physiology, such as the control of cell volume, cell growth or differentiation. On the other hand, [Ca2+]i controls epithelia-specific functions like the regulation of transepithelial solute transport. This short overview addresses the various aspects of Ca2+ signaling in epithelia. It is emphasized that [Ca2+]i is a spatially restricted signal, permitting the distinct regulation of one cellular response. Evidence will be discussed indicating that the functional epithelial polarity is paralleled by polarized membrane receptors and polarized [Ca2+]i signals, regulating the apical and basolateral membranes differentially.