ALT Reactions which can manipulate the connectivity of the molecular skeleton are underexplored as tools for late-stage functionalization, in part because their implementation has been hindered by their often nonintuitive retrosynthetic logic. This presentation will cover selected transformations discovered in our laboratory which address this challenge, enabling single-atom changes through the insertion, deletion, and/or exchange of single heavy atoms (C,N,O, etc.). Our approach to this problem is modality-agnostic, drawing from a wide range of reactive species and synthetic disciplines, but with a significant focus on reagent design and photochemistry. Applications to the synthesis and diversification of complex pharmaceutically relevant compounds as well as unique opportunities for synthesis will be presented alongside mechanistic findings.