<p>Nitrogen-containing heterocycles constitute the pharmacophoric core of the majority of clinically approved small-molecule drugs, yet their conventional synthesis relies on scaffold-specific condensation routes that are poorly suited to late-stage structural diversification. The emergence of single-atom skeletal editing, where one nitrogen atom is inserted directly into an intact aromatic ring to transform scaffold identity without rebuilding the molecular periphery, represents a fundamental departure from traditional heterocycle synthesis and provides a powerful new retrosynthetic logic for medicinal chemistry. This review surveys significant advances in nitrogen atom insertion into aromatic N-heterocycles reported between 2015 and 2025, organized by mechanistic platform. We discuss nitrene-mediated insertion using iodonitrene and sulfenylnitrene reagents, transition-metal-catalysed strategies including copper- and cobalt-catalysed ring expansions and carbon-to-nitrogen transmutation of arenols, electrochemical approaches that eliminate stoichiometric oxidants, and emerging photochemical and photolytic methods that enable late-stage modification of complex substrates. For each platform, substrate scope, functional group tolerance, mechanistic underpinning, and practical limitations are critically evaluated. We further highlight how these strategies collectively enable nitrogen scanning in drug discovery, the systematic replacement of carbon with nitrogen within a lead scaffold to modulate potency, selectivity, and pharmacokinetic properties. Key open challenges including enantioselective nitrogen insertion, predictive regioselectivity, and scalable sustainable synthesis are outlined alongside future directions for this rapidly evolving field.</p>