Inorganic polyphosphate (polyP), a linear polymer of orthophosphoric acid residues, is essential for living cells from bacteria to humans. It forms complexes with metal ions, DNA, and polyhydroxybutyrate. The interaction of polyP with proteins includes polyphosphorylation at lysine and histidine residues, as well as participation in amyloid formation. The enzymes of polyP metabolism are polyfunctional, and their substrates include second messenger compounds and nucleoside phosphates. PolyP is a universal regulatory compound and plays an important role in bone tissue development, thrombosis and inflammation, signal transmission in nerve cells, carcinogenesis, and amyloid formation. PolyP participates in biofilm formation and other processes occurring during the interaction of pathogenic microorganisms with the host. PolyP of the gut microbiome is involved in maintaining intestinal functions. PolyP and the enzymes of its metabolism are promising targets for developing drugs against infections and novel approaches to treat bone, cardiovascular, and neurodegenerative diseases.