Abstract Background Research on the biology of orthodontic tooth movement has led to the prevailing compression-tension theory, which divides the response to orthodontic force into two opposing reactions spatially separated: on the compression side, osteoclasts resorb bone to create space for tooth movement, whereas on the tension side, osteoblasts form bone to restore the alveolar bone structure. Methods Here we take a critical look at the literature on how force-induced inflammation, the periodontal ligament, osteoclasts, and osteoblasts contribute to the biological reaction to orthodontic force. We introduce new evidence that supports a novel theory to explain the biology of tooth movement—the Biphasic Theory. Results The Biphasic Theory of Orthodontic Tooth Movement divides tooth movement into the initial Catabolic Phase, during which osteoclasts resorb bone at both compression and tension sites, and the Anabolic Phase, which occurs subsequently to restore alveolar bone to its pretreatment levels. Conclusions The Biphasic Theory of Tooth Movement successfully addresses shortfalls in the Compression-Tension Theory of Tooth Movement, provides clinicians with a better understanding of how orthodontic forces move teeth, and offers new targets for therapies aimed at accelerating tooth movement.