In this chapter we describe methods for the chemical synthesis of modified nucleosides and nucleotides. Because most naturally nucleosides and nucleotides are commercially available, syntheses have been directed at the generation of nucleosides containing modified bases and sugars and nucleotides in which oxygen atoms in the phosphate ester are replaced by other heteroatoms. The enzymatic processes associated with nucleotide metabolism are described and the roles of nucleotides in biology are discussed. Finally, the biological properties of nucleosides as antiviral and anticancer agents are highlighted.