Since its introduction into dentistry in 1998, CBCT has become increasingly utilized for orthodontic diagnosis, treatment planning and research. The utilization of CBCT for these purposes has been facilitated by the relative advantages of three-dimensional (3D) over two-dimensional radiography. Despite many suggested indications of CBCT, scientific evidence that its utilization improves diagnosis and treatment plans or outcomes has only recently begun to emerge for some of these applications. This article provides a comprehensive and current review of key studies on the applications of CBCT in orthodontic therapy and for research to decipher treatment outcomes and 3D craniofacial anatomy. The current diagnostic and treatment planning indications for CBCT include impacted teeth, cleft lip and palate and skeletal discrepancies requiring surgical intervention. The use of CBCT in these and other situations such as root resorption, supernumerary teeth, temporomandibular joint (TMJ) pathology, asymmetries and alveolar boundary conditions should be justified on the basis of the merits relative to risks of imaging. CBCT has also been used to assess 3D craniofacial anatomy in health and disease and of treatment outcomes including that of root morphology and angulation; alveolar boundary conditions; maxillary transverse dimensions and maxillary expansion; airway morphology, vertical malocclusion and obstructive sleep apnoea; TMJ morphology and pathology contributing to malocclusion; and temporary anchorage devices. Finally, this article utilizes findings of these studies and current voids in knowledge to provide ideas for future research that could be beneficial for further optimizing the use of CBCT in research and the clinical practice of orthodontics.