Pd(II)-catalyzed C–H activation/C–C cross-coupling reactions have emerged as promising catalytic transformations in the past decade. This review discusses the development of these reactions, focusing on the Pd(II)/Pd(0) catalytic cycle for coupling C–H bonds with organometallic reagents. Despite progress, challenges remain in improving the versatility and practicality of these reactions. The review covers various catalytic cycles, including Pd(II)/Pd(0), Pd(II)/Pd(IV), and Pd(0)/Pd(II)/Pd(IV), and highlights their applications in olefination, arylation, and alkylation of sp² and sp³ C–H bonds. Key challenges include regioselectivity, catalyst loading, and enantioselectivity. Recent advances include the use of air as an oxidant, reduced catalyst loading, and novel ligands for selective C–H activation. The review also discusses the potential of these reactions in synthetic chemistry, emphasizing their utility in constructing complex molecules and their relevance to medicinal chemistry. Despite these advancements, further research is needed to enhance efficiency, practicality, and regioselectivity for broader applications.Pd(II)-catalyzed C–H activation/C–C cross-coupling reactions have emerged as promising catalytic transformations in the past decade. This review discusses the development of these reactions, focusing on the Pd(II)/Pd(0) catalytic cycle for coupling C–H bonds with organometallic reagents. Despite progress, challenges remain in improving the versatility and practicality of these reactions. The review covers various catalytic cycles, including Pd(II)/Pd(0), Pd(II)/Pd(IV), and Pd(0)/Pd(II)/Pd(IV), and highlights their applications in olefination, arylation, and alkylation of sp² and sp³ C–H bonds. Key challenges include regioselectivity, catalyst loading, and enantioselectivity. Recent advances include the use of air as an oxidant, reduced catalyst loading, and novel ligands for selective C–H activation. The review also discusses the potential of these reactions in synthetic chemistry, emphasizing their utility in constructing complex molecules and their relevance to medicinal chemistry. Despite these advancements, further research is needed to enhance efficiency, practicality, and regioselectivity for broader applications.