Orthodontic tooth movement (OTM) is now recognized as a biologically mediated process involving interactions between mechanical forces and cellular responses in the periodontium. Key mediators include cytokines, prostaglandins, and the RANK/RANKL/OPG system, which regulate bone remodeling through osteoclast and osteoblast activity. The concept of the regional acceleratory phenomenon (RAP) has led to the development of procedures such as corticotomy, piezocision, and micro-osteoperforations to accelerate tooth movement. Additionally, biochemical approaches including pharmacological agents, stem cell therapy, and low-level laser therapy have been explored to enhance biological responses. These advances integrate biological insights with biomechanics, aiming to achieve more efficient and patient-friendly orthodontic treatment.