Abstract
The advent of bioorthogonal chemistry has transformed scientific research, offering a powerful tool for selective and noninvasive labeling of (bio)molecules within complex biological environments. This innovative approach has facilitated the study of intricate cellular processes, protein dynamics, and interactions. Nevertheless, a number of challenges remain to be addressed, including the need for improved reaction kinetics, enhanced biocompatibility, and the development of a more diverse and orthogonal set of reactions. While scientists continue to search for veritable solutions, bioorthogonal chemistry remains a transformative tool with a vast potential for advancing our understanding of biology and medicine. This Perspective offers insights into reactions commonly classified as "bioorthogonal", which, however, may not always demonstrate the desired selectivity regarding the interactions between their components and the additives or catalysts used under the reaction conditions.