This minireview focuses on the chemoselectivity of C–H bond oxidation reactions, emphasizing the role of substrate characteristics rather than reagent scope. It highlights the importance of inductive effects, conjugation, hyperconjugation, steric hindrance, and strain release in determining the reactivity of sp² and sp³ C–H bonds. The review discusses various examples of how these factors influence the selectivity of oxidation reactions, including the oxidation of alkane substrates, cyclopropanes, and heteroatom-containing compounds. It also explores the impact of steric effects and strain release on the rate and selectivity of C–H bond oxidation. Additionally, the review covers directed oxidations using directing groups and the activation of sp² centers. The case studies section provides detailed examples of complex systems, such as bicyclic and polycyclic compounds, to illustrate the challenges and opportunities in achieving site-selective C–H bond oxidation.This minireview focuses on the chemoselectivity of C–H bond oxidation reactions, emphasizing the role of substrate characteristics rather than reagent scope. It highlights the importance of inductive effects, conjugation, hyperconjugation, steric hindrance, and strain release in determining the reactivity of sp² and sp³ C–H bonds. The review discusses various examples of how these factors influence the selectivity of oxidation reactions, including the oxidation of alkane substrates, cyclopropanes, and heteroatom-containing compounds. It also explores the impact of steric effects and strain release on the rate and selectivity of C–H bond oxidation. Additionally, the review covers directed oxidations using directing groups and the activation of sp² centers. The case studies section provides detailed examples of complex systems, such as bicyclic and polycyclic compounds, to illustrate the challenges and opportunities in achieving site-selective C–H bond oxidation.