The article discusses the recent advancements in catalytic C–H functionalization reactions, particularly those involving metal carbenes and nitrenes. These reactions offer new strategic approaches for the synthesis of complex natural products and pharmaceutical agents by selectively modifying carbon-hydrogen bonds. The authors highlight the advantages of these methods, including high turnover numbers and selectivity in regioselectivity and stereoselectivity. They also review specific examples of successful applications, such as the enantioselective synthesis of (R)-(-)-baclofen and (R)-(-)-rolipram, and the synthesis of pharmaceutical agents like Ritalin. The article further explores the potential of donor/acceptor functionalized carbenoids for enantioselective intermolecular C–H insertion and the use of chiral catalysts to enhance selectivity. Additionally, it discusses the application of C–H amination by metal nitrenoids in the synthesis of complex natural products, such as manzacidin A and (+)-saxitoxin. The authors conclude by emphasizing the rapid expansion of this field and its potential as an enabling technology in drug discovery and synthesis.The article discusses the recent advancements in catalytic C–H functionalization reactions, particularly those involving metal carbenes and nitrenes. These reactions offer new strategic approaches for the synthesis of complex natural products and pharmaceutical agents by selectively modifying carbon-hydrogen bonds. The authors highlight the advantages of these methods, including high turnover numbers and selectivity in regioselectivity and stereoselectivity. They also review specific examples of successful applications, such as the enantioselective synthesis of (R)-(-)-baclofen and (R)-(-)-rolipram, and the synthesis of pharmaceutical agents like Ritalin. The article further explores the potential of donor/acceptor functionalized carbenoids for enantioselective intermolecular C–H insertion and the use of chiral catalysts to enhance selectivity. Additionally, it discusses the application of C–H amination by metal nitrenoids in the synthesis of complex natural products, such as manzacidin A and (+)-saxitoxin. The authors conclude by emphasizing the rapid expansion of this field and its potential as an enabling technology in drug discovery and synthesis.