The unfolding of science behind the biology of orthodontic tooth movement (OTM) has been slow and tedious. Orthodontic research has followed closely the scientific footsteps imprinted by biologists and physicians. The orthodontic appliance is the clinician's primary tool for initiating and sustaining the biological processes that control tooth movement. The cascade of biological events that induce orthodontic tooth movement is initiated by mechanical stresses in the periodontium. Forces are transferred to the teeth by the clinician using appliances designed to displace teeth a prescribed amount in a desired direction. This sends signals to the cells to remodel tissues in a way that allows teeth to move. To interpret the biological responses to activation of any orthodontic appliance, each interface in the process must be thoroughly understood.