Oligonucleotides and their analogues have recently found broad application in biochemistry and molecular biology as new tools for studying interactions of nucleic acids with other biomolecules, and as potential candidates for therapeutics. In this chapter the synthetic methods leading to P-chiral oligonucleotide analogues are reviewed, including synthesis of isotopomeric phosphates and various nucleotide and oligonucleotide conjugates. In this respect special emphasis has been put on the application of oxathiaphospholane methodology, recently developed in the authors’ laboratory, for the stereocontrolled synthesis of P-chiral biophosphate analogues.