Early in eukaryotic evolution, the cell has evolved a considerable inventory of proteins engaged in the regulation of intracellular Ca2+ concentrations, not only to avoid toxic effects but beyond that to exploit the signaling capacity of Ca2+ by small changes in local concentration. Among protozoa, the ciliate Paramecium may now be one of the best analyzed models. Ciliary activity and exo-/endocytosis are governed by Ca2+, the latter by Ca2+ mobilization from alveolar sacs and a superimposed store-operated Ca2+-influx. Paramecium cells possess plasma membrane- and endoplasmic reticulum-resident Ca2+-ATPases/pumps (PMCA, SERCA), a variety of Ca2+ influx channels, including mechanosensitive and voltage-dependent channels in the plasma membrane, furthermore a plethora of Ca2+-release channels (CRC) of the inositol 1,4,5-trisphosphate and ryanodine receptor type in different compartments, notably the contractile vacuole complex and the alveolar sacs, as well as in vesicles participating in vesicular trafficking. Additional types of CRC probably also occur but they have not been identified at a molecular level as yet, as is the equivalent of synaptotagmin as a Ca2+ sensor for exocytosis. Among established targets and sensors of Ca2+ in Paramecium are calmodulin, calcineurin, as well as Ca2+/calmodulin-dependent protein kinases, all with multiple functions. Thus, basic elements of Ca2+ signaling are available for Paramecium.