Biocompatible bond-cleavage reactions have expanded the repertoire of bioorthogonal tools substantially, providing methods beyond chemical ligation to control the function of (bio)molecules in biological environments and living systems. Bioorthogonal elimination has been achieved by applying transition metals or click-type reactions to trigger the cleavage of a linker and/or the release of a molecule. So far, these methods have mainly been applied to chemically control (i) the cleavage of ligand-drug conjugates and (ii) the activation of prodrugs, thereby facilitating the release of therapeutic molecules. In addition, strategies to activate caged proteins ('turn-on') and to cleave imaging probes ('turn-off') have been designed, expanding the overall scope of bioorthogonal ON/OFF control.