Would you like to tune the reactivity of your protein? Genetically encoded, site-specific incorporation of non-proteinogenic amino acids provides unprecedented molecular control over proteins and therefore advances the chemical biology capabilities of biochemical studies and biomaterials. In order to engineer proteins with non-proteinogenic amino acids the machinery of translation is expanded using synthetic biology concepts. Using this technology Oregon State University has started the first Unnatural Protein Facility. The UP Facility mission is to develop the technology of non-proteinogenic amino acids incorporation in order to advance biochemistry, biotechnology and nanotechnology. The advances in reengineering translation for in vivo protein studies and use of site-specific incorporation of unique chemical functionalities for chemical biology will be discussed. Additionally, the considerable expansion of non-proteinogenic amino acids available due to advances in increasing synthetase permissivity will be presented.