Base transformation chemistry with naturally occurring purine nucleosides began in the 1950s. This approach retains the (regio and stereo)chemical integrity of the enzymatically synthesized nucleic acid components. Discovery of new reactions and new developments in transformation chemistry methodology have provided expanded opportunities for conversion of nucleic acid components into significantly modified entities. An overview of such chemistry (at C2 and C6) beginning with purine nucleosides that are found in nucleic acids will be presented with emphasis on efforts in our laboratory and closely related studies.