Immobilization of proteins onto surfaces is of great importance in numerous applications, including protein analysis, drug screening, and medical diagnostics, among others. The success of all these technologies relies on the immobilization technique employed to attach a protein to the corresponding surface. Non‐specific physical adsorption or chemical cross‐linking with appropriate surfaces results in the immobilization of the protein in random orientations. Site‐specific covalent attachment, on the other hand, leads to molecules being arranged in a definite, orderly fashion and allows the use of spacers and linkers to help minimize steric hindrances between the protein and the surface. The present work reviews the latest chemical and biochemical developments for the site‐specific covalent attachment of proteins onto solid supports. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 450–458, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com