This chapter focuses on the chemistry underlying self-healing materials, exploring the various mechanisms that enable materials to repair themselves autonomously. It discusses dynamic bonding mechanisms, including reversible covalent bonds (such as Diels–Alder reactions and disulfide exchange), non-covalent interactions (e.g., hydrogen bonding, ionic interactions, and van der Waals forces), and supramolecular chemistry, all of which play crucial roles in healing processes. The chapter also delves into the use of chemical catalysts, such as photo-initiators and redox systems, which facilitate the healing process in polymers and composites. Additionally, it examines the applications of stimuli-responsive healing systems, activated by external triggers like light, temperature, and pH, to enhance the performance and adaptability of self-healing materials. Throughout the chapter, case studies highlight the diverse applications of chemistry-based self-healing systems, from aerospace and automotive to biomedical fields. Challenges in scaling up these technologies, as well as their environmental stability, are discussed alongside opportunities for advancing the chemical design of self-healing materials. The chapter concludes with a forward-looking perspective on how new chemical approaches and interdisciplinary collaboration can overcome current limitations, offering a roadmap for the future development of more efficient, cost-effective, and resilient self-healing materials.