Chemical biology research often requires precise covalent attachment of tags to the proteins. Such methods enable bioimaging , biophysical investigations , disease diagnosis and protein-based therapeutics. In this perspective, we have been investing efforts to address three questions. (a) How does the protein behave as a substrate in a chemical transformation? (b) Can we develop chemical methods for single-site modification of native proteins? (c) Is it possible to have a modular chemical method for precision labeling of proteins? The first step of our research hinges on the development of transformations that would befriend protein - compatible parameters. The critical challenge relates to the chemoselectivity and site -selectivity. In other words, identification of principles that would allow us to generate reactivity biases at specific sites of the protein. In this perspective, we have developed methods for : (a) utilization of N-terminus alpha amine as a reactivity hotspot, (b) targeting the most reactive Lys residues through transient protection of alpha amine, and (c) modular linchpin directed modification for labeling single His or Lys residue. These technologies deliver single -site installation of various probes in native proteins. The user-friendly protocols result in analytically pure labeled proteins. The structure, enzymatic activity, binding to receptors, and downstream signaling pathways are typically unaffected. Also, these technologies allow access to homogeneous antibody -drug conjugates for directed cancer chemotherapeutics. Along with these developments, I would discuss the analytical kits developed in our laboratory for expediting the unambiguous analysis of the labeled proteins.