Orthodontic tooth movement differs significantly from the physiological tooth movement, as it determines a biological response of the surrounding tissues of the teeth, resulting in a remodelling of the periodontal ligament and the alveolar bone. The result is a biochemical adaptive response to the application of the orthodontic force with the reorganization of the intracellular and the extracellular matrix, in addition to a change of the local vascularization. This in turn leads to the synthesis and the release of arachidonic acid, growth factors, metabolites, cytokines and various enzymes. Biologically, not only the intensity of the force, but also its duration and the tissue response to the application of the same are important for tooth movement. Having these insights it will possible to examine the concept of optimal orthodontic force, a determining factor for the success of orthodontic treatment. The purpose of this revision was to describe the biological processes and future perspective of the application of orthodontic force, by providing relevant information to understand the changes at the molecular and cellular level occurring when the tissues are subjected to such forces. Knowledge on the subject of mechanics and biology in orthodontics is constantly growing, producing an increasingly strong basis for clinical success.