Centric relation (CR) is one of the core research contents in orthodontics, prosthodontics, and gnathology, acting as an important physiological factor in reconstructing the occlusion and adjusting the occlusal relationship. For over a century, CR is still a controversial subject in dentistry. CR has been redefined for several times, and recently, its application has been widened in orthodontics, including orthodontic diagnosis, clinical examination and analysis, and treatment goals. The purpose of this article is to review the definition of CR, its relationship with malocclusion, and the application of this relationship in orthodontic treatment.