Remodeling changes in paradental tissues are considered essential in effecting orthodontic tooth movement. The force-induced tissue strain produces local alterations in vascularity, as well as cellular and extracellular matrix reorganization, leading to the synthesis and release of various neurotransmitters, cytokines, growth factors, colony-stimulating factors, and metabolites of arachidonic acid. Recent research in the biological basis of tooth movement has provided detailed insight into molecular, cellular, and tissue-level reactions to orthodontic forces. Although many studies have been reported in the orthodontic and related scientific literature, a concise convergence of all data is still lacking. Such an amalgamation of the rapidly accumulating scientific information should help orthodontic clinicians and educators understand the biological processes that underlie the phenomenon of tooth movement with mechanics (removable, fixed, or functional appliances). This review aims to achieve this goal and is organized to include all major findings from the beginning of research in the biology of tooth movement. It highlights recent developments in cellular, molecular, tissue, and genetic reactions in response to orthodontic force application. It reviews briefly the processes of bone, periodontal ligament, and gingival remodeling in response to orthodontic force. This review also provides insight into the biological background of various deleterious effects of orthodontic forces.