Direct selective palladium catalyzed C-H functionalization has become a highly attractive strategy in organic synthesis and represents a highly desirable goal. Compared with cross-coupling reactions of C-H bonds with aryl or alkyl halides/pseudohalides, the strategy of cross-coupling reactions of C-H bonds with organometallic reagents is of great significance and obvious advantages. This feature article provides a comprehensive summary of recent advances and an intensive analysis on Pd-catalyzed C-H activation and oxidative coupling with various organometallic reagents.