In most cell types, hyposmotic swelling consistently elicits an increase in the concentration of cytosolic Ca<sup>2+</sup> – [Ca<sup>2+</sup>]<sub>i</sub> – with contributions of extracellular and intracellular sources. The mechanisms of Ca<sup>2+</sup> entry and release from endogenous sources are not fully clarified and may be cell specific. The ubiquity of the swelling-evoked [Ca<sup>2+</sup>]<sub>i</sub> rise makes Ca<sup>2+</sup> a likely candidate for a role as osmotransducing signal. However, the regulatory volume decrease (RVD) which follows swelling and the osmolyte fluxes involved in this process are not always Ca<sup>2+</sup> dependent. It was found that, with a few exceptions, in most cell types the osmosensitive Cl<sup>–</sup> efflux pathway and the swelling-activated organic osmolyte fluxes are Ca<sup>2+</sup> independent. In contrast, Ca<sup>2+</sup>-dependent or Ca<sup>2+</sup>-independent K<sup>+</sup> fluxes activated by swelling are detected, depending on the cell type. The close correlation found in this review between the Ca<sup>2+</sup> dependence of RVD and that of the K<sup>+</sup> channels activated by swelling led to the conclusion that it is the type of osmosensitive K<sup>+</sup> pathway which largely confers the Ca<sup>2+</sup> dependence to RVD. Interestingly, this coincidence of Ca<sup>2+</sup>-dependent K<sup>+</sup> efflux and RVD is found predominantly in epithelial cells, whereas in nonepithelial cells both processes are largely Ca<sup>2+</sup> independent. In these cells, the [Ca<sup>2+</sup>]<sub>i</sub> rise elicited by swelling may be an epiphenomenon.