Inorganic polyphosphates (PolyP) are linear polymers containing a few to several hundred orthophosphate residues linked by energy-rich phosphoanhydride bonds. Until quite recently, they were considered molecular fossils, ATP precursors in the evolution of living cells, and phosphorus storage in microorganisms. Now it has been established that PolyPs and polyphosphate kinases are involved in switching the genetic programs of bacterial cell survival under stationary stage and stresses. In human organism, PolyPs are involved in the regulation of Ca²⁺ uptake in mitochondria, bone tissue development, blood coagulation and cancerogenesis. The properties of polyphosphate kinases, exopolyphosphatases, endopolyphosphatases and other enzymes of PolyP biosynthesis and utilization in prokaryotic and eukaryotic cells, as well as their multiple functions are considered in this review. High similarities in properties and amino acid sequences of some yeast and human PolyP-metabolizing enzymes are discussed.