The recent discovery of bioorthogonal click chemistry has created a new field in chemical biology in which biomolecules that are not directly encoded in the genome can be monitored in living systems.[1] By hijacking a cell's biosynthetic machinery, a metabolic precursor functionalized with a bioorthogonal chemical tag is incorporated into target biomolecules, including glycans,[2] lipids,[3] proteins,[4] and nucleic acids.[5] Subsequently, a tailordesigned click reaction is employed to conjugate a complementary biophysical probe, which enables visualization [2] or enrichment of the target biomolecules for molecular identification.[6, 7] Though both applications require exquisite selectivity to maximize signal to noise ratio, each has specific criteria to meet. For dynamic imaging studies, not only must the employed reaction proceed rapidly at physiological conditions to allow monitoring of events taking place on the minute time scale, it must also be nontoxic and non-interfering with the surrounding cellular milieu.[2, 8] Contrarily, molecular identification applications, eg proteomics analysis, prioritize sensitivity over biocompatibility—in most cases only limited amounts of samples are available for analysis and the targets of interest may be low in abundance. Thus, reactions that enjoy fast kinetics at low substrate concentration (eg micromolar) are preferred. In view of these requirements, the choice of a tailored chemical tag and chemistry for a specific bioconjugation process is not trivial.