The late-stage functionalization and diversification of complex structures including biomolecules is often achieved with the help of click chemistry. Besides employing irreversible click-like reactions, many synthetic applications benefit from reversible clicking strategies, so called de-/trans-click approaches. Yet, the combination of both, reversible and irreversible click chemistry – while still respecting the stringent criteria of click transformations – remains so far elusive for modifications of high value structures. Here, we report click’n lock as a concept that enables reversible clicking and on-demand locking of chemical entities, thus switching from reversible to irreversible modifications of complex (bio)molecules. For this purpose, we employ the tetrazine – thiol exchange (TeTEx) reaction as a fully traceless click reaction with second order rate constants k2 up to 25 M-1 s-1 within aqueous environments. Employing TeTEx as a reversible click reaction for the chemoselective modification of biomolecules is made possible by the use of asymmetric 3,6-tetrazines bearing a single sulfide residue. The inherent reactivity of tetrazines towards inverse electron demand Diels – Alder (IEDDA) reactions allows to stabilize the clicked structure, switching from reversible to irreversible systems (click’n lock).