The article reviews the development and application of rhodium-catalyzed C-H bond activation for the synthesis of complex molecules. Rhodium catalysts are particularly noted for their functional group tolerance and wide synthetic utility. The review highlights two mechanistically distinct reaction pathways: one where the heteroatom acts as a chelator to bind the Rh catalyst, and another where the heteroatom initially coordinates the Rh catalyst and then stabilizes the formation of a metal-carbon bond. The article discusses the synthesis of complex molecules from simple precursors, emphasizing the importance of selectivity in C-H bond functionalization methods. It covers various applications, including the synthesis of natural products and drug candidates, such as a tricyclic mescaline analogue and (+)-lithospermic acid. The review also explores stereoselective alkylation using chiral auxiliaries and enantioselective intramolecular alkylation with chiral phosphoramidite ligands. Additionally, it examines directed alkenylation and arylation reactions, as well as carbonylation, highlighting the challenges and advancements in these areas. The article concludes by discussing the underexplored potential of olefin functionalization using chelation assistance.The article reviews the development and application of rhodium-catalyzed C-H bond activation for the synthesis of complex molecules. Rhodium catalysts are particularly noted for their functional group tolerance and wide synthetic utility. The review highlights two mechanistically distinct reaction pathways: one where the heteroatom acts as a chelator to bind the Rh catalyst, and another where the heteroatom initially coordinates the Rh catalyst and then stabilizes the formation of a metal-carbon bond. The article discusses the synthesis of complex molecules from simple precursors, emphasizing the importance of selectivity in C-H bond functionalization methods. It covers various applications, including the synthesis of natural products and drug candidates, such as a tricyclic mescaline analogue and (+)-lithospermic acid. The review also explores stereoselective alkylation using chiral auxiliaries and enantioselective intramolecular alkylation with chiral phosphoramidite ligands. Additionally, it examines directed alkenylation and arylation reactions, as well as carbonylation, highlighting the challenges and advancements in these areas. The article concludes by discussing the underexplored potential of olefin functionalization using chelation assistance.