The chapter discusses the development and applications of palladium-catalyzed ligand-directed C–H functionalization reactions, which are crucial for converting carbon-hydrogen bonds into various functional groups such as carbon-oxygen, carbon-halogen, carbon-nitrogen, carbon-sulfur, and carbon-carbon bonds. These reactions are significant for their potential in synthesizing pharmaceuticals, natural products, agrochemicals, polymers, and feedstock commodity chemicals. The challenges in C–H functionalization include the inert nature of carbon-hydrogen bonds and the need to control site selectivity in complex molecules. Transition metals, particularly palladium, have been extensively studied for their ability to activate C–H bonds and form new functional groups under mild conditions. The review focuses on the mechanisms and applications of palladium-catalyzed C–H functionalization, emphasizing the versatility of palladium catalysts in installing different types of bonds. Key mechanisms involve C–H activation at PdII centers, followed by reductive elimination or electrophilic cleavage of the Pd–C bond. The chapter details various oxidants used for C–H oxygenation, including iodine(III), iodine(I), peroxides, and dioxygen, each with its own advantages and limitations. For carbon-sulfur bond formation, the chapter highlights the use of Pd(cod)Cl2 for converting thioenols to benzothiophenes and the role of disulfide intermediates. Carbon-halogen bond formation is discussed with examples using N-halosuccinimides, copper halides, and Suárez reagents, emphasizing the importance of directing groups and oxidants. The section on carbon-fluorine bond formation mentions two reported examples using Selectfluor® and N-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate. Carbon-nitrogen bond formation is explored through intramolecular and intermolecular C–N coupling, with examples involving carbazoles, indazoles, and diarylindoles. Finally, the chapter covers carbon-carbon bond formation, including ortho-arylation, alkenylation, and alkynylation, with a focus on the use of pre-functionalized arylating agents and direct oxidative coupling reactions. The mechanisms and conditions for these transformations are discussed, highlighting the importance of directing groups and catalyst optimization.The chapter discusses the development and applications of palladium-catalyzed ligand-directed C–H functionalization reactions, which are crucial for converting carbon-hydrogen bonds into various functional groups such as carbon-oxygen, carbon-halogen, carbon-nitrogen, carbon-sulfur, and carbon-carbon bonds. These reactions are significant for their potential in synthesizing pharmaceuticals, natural products, agrochemicals, polymers, and feedstock commodity chemicals. The challenges in C–H functionalization include the inert nature of carbon-hydrogen bonds and the need to control site selectivity in complex molecules. Transition metals, particularly palladium, have been extensively studied for their ability to activate C–H bonds and form new functional groups under mild conditions. The review focuses on the mechanisms and applications of palladium-catalyzed C–H functionalization, emphasizing the versatility of palladium catalysts in installing different types of bonds. Key mechanisms involve C–H activation at PdII centers, followed by reductive elimination or electrophilic cleavage of the Pd–C bond. The chapter details various oxidants used for C–H oxygenation, including iodine(III), iodine(I), peroxides, and dioxygen, each with its own advantages and limitations. For carbon-sulfur bond formation, the chapter highlights the use of Pd(cod)Cl2 for converting thioenols to benzothiophenes and the role of disulfide intermediates. Carbon-halogen bond formation is discussed with examples using N-halosuccinimides, copper halides, and Suárez reagents, emphasizing the importance of directing groups and oxidants. The section on carbon-fluorine bond formation mentions two reported examples using Selectfluor® and N-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate. Carbon-nitrogen bond formation is explored through intramolecular and intermolecular C–N coupling, with examples involving carbazoles, indazoles, and diarylindoles. Finally, the chapter covers carbon-carbon bond formation, including ortho-arylation, alkenylation, and alkynylation, with a focus on the use of pre-functionalized arylating agents and direct oxidative coupling reactions. The mechanisms and conditions for these transformations are discussed, highlighting the importance of directing groups and catalyst optimization.