This chapter starts by providing a historical background of our research endeavors, spanning over the past half-century and dedicated to developing various isotope-aided methods in biological NMR spectroscopy. The focus then shifts to the stereo-array isotope labeling (SAIL) method, a recent milestone advancing stable-isotope labeling NMR technologies for structural studies of proteins from diverse perspectives. This advancement includes accurate structural determinations of large proteins, elaboration for automated structural determination, highly efficient and versatile residue- and stereo/regio-specific methyl labeling using newly developed auxotrophic E. coli strains, and the revelation of large amplitude slow breathing motion (LASBM) through the aromatic ring-flipping of residues in ligand binding interfaces. We also expand the discussion on the applications of deuterium-induced 13C-NMR isotope shift to investigate hydrogen exchange phenomena in side-chain polar groups. These approaches have proven highly valuable for studying the structural and biological significance of polar side-chain groups in various amino acid residues. Simultaneously, the anticipated role of NMR spectroscopy is rapidly transitioning from structure determinations to dynamic studies of biologically interesting targets, such as membrane proteins and supra-molecular protein complexes. The dynamic aspects of protein–protein and protein–ligand interactions, crucial for understanding their biological functions, can be efficiently explored using protein residue selectively labeled with amino acids featuring optimized labeling patterns. We briefly describe our latest studies on aromatic amino acid residues in larger proteins. Consequently, we maintain absolute confidence that biological NMR spectroscopy will continue to evolve with further innovations in isotope labeling technologies in the upcoming era, characterized by ultrahigh-field spectrometers beyond 1 GHz.