Life's complexity and organization are illustrated in the biological phenomena underlying orthodontic tooth movement (OTM). Orthodontic tooth movement is essentially a biologic reaction towards a mechanical force. It is based on the premise that when force is delivered to a tooth and thereby transmitted to the adjacent investing tissues, certain mechanical, chemical and cellular events take place within these tissues, which allow for structural alterations and contribute to the movement of that tooth.To better understand orthodontic movement, we need to understand the tissue phenomena that occur at each stage of tooth movement. With a thorough knowledge of the biochemical mediators of orthodontic tooth movement and their mechanisms will provide a rational for better and effective treatment by minimizing the risks of root resorption, optimizing the treatment and comfort of the patient.