Acyclic nucleoside phosphonates (ANPs) are important biologically active nucleotide analogs. They contain an isopolar phosphonomethyl function linked to the hydroxyl group of an acyclic side-chain via an undegradable ether group. Though their most important activity is antiviral, some exhibit cytostatic or antiprotozoic effects. The three most important groups of ANP are presented here as synthetic procedures for a large laboratory scale. Synthesis follows three principles: (1) introduction of a protected phosphonomethyl group to the hydroxyl on an appropriate alkyl side-chain of an acyclic nucleoside, (2) alkylation of the heterocyclic base by a synthon with all characteristic features of the future phoshonate-bearing side-chain, or (3) transformation of a reactive group at the heterocyclic base. The last step in all these cases is removal of the phosphonate esters. Preparation methods are described in detail for PMEA, PMEG, PMEDAP and its N(6)-cyclopropyl derivative, (R)-PMPA, and (S)-HPMPA, as well as all intermediates and synthons.