Although functional appliances have been widely adopted for clinical modulation of mandibular growth for nearly a century, the underlying regulatory mechanism of mandibular condyle growth have been under investigation. Over these years, studies have been focused on both the natural growth of mandibular condyle and its growth modulation by functional appliances at cellular and molecular levels. It has been identified that several factors including Sox9, type II collagen, PTHrP, Ihh, FGFR, type X collagen, VEGF, Cbfa1/Runx2 and OPG/RANKL play a pivotal role in growth and development of mandibular condyle. This review provides an overview of the impacts of these key factors on mandibular condylar growth.published_or_final_versio