Several studies have indicated a positive response of the temporomandibular joint (TMJ) to mandibular advancement, while others have reported that TMJ adaptive responses are non-existent and negligible. Controversy continues to grow over the precise nature of skeletal changes that occur during mandibular growth modification, due to an apparent lack of tissue markers required to substantiate the precise mechanism by which this is occurring. However, evidence suggests that orthopedic forces clinically modify the growth of the mandible. To further our knowledge about the effect of orthopedic treatment on the TMJ, it is necessary that we understand the biologic basis behind the various tissues involved in the TMJ's normal growth and maturation. The importance of this knowledge is to consider the potential association between TMJ remodeling and mandibular repositioning under orthopedic loading. Considerable histologic and biochemical research has been performed to provide basic information about the nature of skeletal growth modification in response to mandibular advancement. In this review, the relevant histochemical evidence and various theories regarding TMJ growth modification are discussed. Furthermore, different regulatory growth factors and tissue markers, which are used for cellular and molecular evaluation of the TMJ during its adaptive response to biomechanical forces, are underlined.