Protein phosphatases (PP), the antagonists of protein kinases, are essential regulatory elements in all eukaryotes. According to their substrate specificity they are classified as Ser/Thr, Tyr and dual specificity protein phosphatases. The former can be divided into type 1 and 2 based on biochemical criteria. However, the advent of molecular cloning techniques revealed that PP1, PP2A and PP2B belong to one big superfamily of enzymes, while PP2C represents a distinct group of phosphatases. In addition, a large number of so called novel phosphatases havs been cloned. Interestingly, the ammo acid sequence of the catalytic core within the catalytic subunits, as well as some parts of the regulatory subunits are well conserved in different species. This fact indicates the significance of the proteins, and permits a homology based cloning strategy. Several experimental model organisms have been used to discern the physiological functions of each separate member in the enzyme family. It turned out that Ser/Thr protein phosphatases played an essential role in the regulation of cell cycle, signal transduction, metabolism, osmotic stability, modulation of neuronal activity; and the list is far from being complete. The results of biochemical, molecular biology and generic approaches will be summarized with the main emphases on the comparison between the phosphatases obtained from different organisms.