There is a large interest in the use of nucleic acids covalently bound to surfaces for a variety of biomedical uses: biosensors, microarrays, drug delivery, lab-on-chip devices, and gene therapy, etc. Most of these applications require the covalent attachment of oligonucleotides via specific reactive groups on both modified oligonucleotide and/or surface. The purpose of this chapter is to provide experimental protocols for the synthesis of oligonucleotides and for the immobilization of these synthetic oligonucleotides onto surfaces such as gold and silicon oxide.