a | Strained alkynes enable copper-free catalysis of cycloaddition to dipoles such as azides. b | The fastest biorthogonal reaction involves the inverse-electron demand [4 + 2] addition between a tetrazine and a dienophile. BARAC, biarylazacyclooctynone; BCN, bicyclo[2.1.0]nonyne; DIBO, dibenzocyclooctyne; DIFO, difluorinated cyclooctyne; k2, second-order rate constant; OCT, cyclooctyne; TMTH, 3,3,6,6-tetramethylthiaheptyne.