This review is aimed at biochemists and molecular biologists, and covers the chemistry and key features involved in the solid-phase synthesis of a variety of the better known DNA and RNA analogues by the phosphoramidite and H-phosphonate methods. A wide spectrum of biological applications such as inhibition of gene expression, translation arrest, RNA processing, affinity purification of RNA-protein complexes, in situ hybridization, and synthetic ribozymes are then discussed in some detail, enabling the molecular biologist to get an idea of what is possible using the current technology.