The direct functionalization of C-H bonds is a crucial transformation in organic synthesis; however, reliance on precious transition-metal catalysts presents economic and environmental challenges. This talk will highlight our decadelong research program, which has developed sustainable, transition-metal-free strategies for the C(sp²)-H functionalization of biologically relevant scaffolds. By designing novel reagent systems as well as harnessing alternative energy inputs-including photochemistry, electrochemistry, and microwave/ultrasound irradiations-we have established efficient protocols for regioselective CHalogen (X = Cl, Br, I), C-Chalcogen (S, Se, Te), and C-Nitrogen bond formation. Our interest in green chemistry principles, employing benign reagents, minimizing energy consumption, and reducing waste, is to provide practical and powerful alternatives for the late-stage diversification of complex molecules.