The recent advent of transition-metal mediated C-H activation is revolutionizing the synthetic field and gradually infusing a "C-H activation mind-set" in both students and practitioners of organic synthesis. As a powerful testament of this emerging synthetic tool, applications of C-H activation in the context of total synthesis of complex natural products are beginning to blossom. Herein, recently completed total syntheses showcasing creative and ingenious incorporation of C-H activation as a strategic manoeuver are compared with their "non-C-H activation" counterparts, illuminating a new paradigm in strategic synthetic design.