This review article by T. Gensch, M. N. Hopkinson, F. Glorius, and J. Wencel-Delord provides an overview of the current state of mild metal-catalyzed C–H activation reactions. The authors highlight the progress made since 2011 in developing efficient and selective transformations that proceed at or below ambient temperature, without the need for strong acidic or basic additives, or strong oxidants. The review is structured into four main sections, each focusing on different aspects of C–H activation: 1. **Tuning of the Catalyst's Properties**: The role of the catalyst in determining the mildness of C–H activation reactions is emphasized. The electronic and steric properties of the catalyst, such as the identity and oxidation state of the metal, are crucial. High-valent metals like Pd, Rh, Ir, and Ru typically undergo electrophilic pathways, while low-valent metals like Rh and Ir often undergo oxidative addition. 2. **Substrate Molecule**: The impact of directing groups and the choice of substrates on the C–H activation step is discussed. Strongly coordinating directing groups can improve binding to the catalyst, while weakly coordinating groups can enhance the subsequent functionalization step. 3. **Internal Oxidants**: The use of internal oxidants, such as oxygen, can facilitate oxidative transformations without the need for external oxidants, contributing to the mildness of the reaction. 4. **Oxidative C–H Coupling Reactions**: The review also covers oxidative C–H coupling reactions that avoid strong external oxidants, further enhancing the mildness of these transformations. The article includes detailed examples of mild C–H activation reactions, particularly those involving Pd, Rh, Ir, and Ru catalysts, and discusses the mechanisms and strategies that have led to these advancements. The authors aim to provide a comprehensive guide for the design of future C–H transformations and inspire the next generation of mild reactions.This review article by T. Gensch, M. N. Hopkinson, F. Glorius, and J. Wencel-Delord provides an overview of the current state of mild metal-catalyzed C–H activation reactions. The authors highlight the progress made since 2011 in developing efficient and selective transformations that proceed at or below ambient temperature, without the need for strong acidic or basic additives, or strong oxidants. The review is structured into four main sections, each focusing on different aspects of C–H activation: 1. **Tuning of the Catalyst's Properties**: The role of the catalyst in determining the mildness of C–H activation reactions is emphasized. The electronic and steric properties of the catalyst, such as the identity and oxidation state of the metal, are crucial. High-valent metals like Pd, Rh, Ir, and Ru typically undergo electrophilic pathways, while low-valent metals like Rh and Ir often undergo oxidative addition. 2. **Substrate Molecule**: The impact of directing groups and the choice of substrates on the C–H activation step is discussed. Strongly coordinating directing groups can improve binding to the catalyst, while weakly coordinating groups can enhance the subsequent functionalization step. 3. **Internal Oxidants**: The use of internal oxidants, such as oxygen, can facilitate oxidative transformations without the need for external oxidants, contributing to the mildness of the reaction. 4. **Oxidative C–H Coupling Reactions**: The review also covers oxidative C–H coupling reactions that avoid strong external oxidants, further enhancing the mildness of these transformations. The article includes detailed examples of mild C–H activation reactions, particularly those involving Pd, Rh, Ir, and Ru catalysts, and discusses the mechanisms and strategies that have led to these advancements. The authors aim to provide a comprehensive guide for the design of future C–H transformations and inspire the next generation of mild reactions.