Craniofacial profile, maxilla-mandibular relations, dento- alveolar bone discrepancies, skeletal maturation and dental asymmetries are important elements of an orthodontic and orthognathic diagnosis and treatment planning. For proper position and angulation of teeth, orthognathic surgery aims to correct dental crowding, spacing, misalignment and rotations of teeth, via tooth/teeth extractions for example, as part of the umbrella orthodontic and orthognathic interventional treatment plan. Indeed, exodontia is often needed to relieve moderate to severe crowding (arch- length discrepancies) and create the needed space for the proper alignment of the dentition and eventual functional occlusion. Herein, first and second premolar extractions are often prescribed, preferably when other methods have been exhausted. Yet the discussion regarding the use of premolar extractions is not whether exodontia should be performed, yet rather what malocclusion class, tooth-size and tooth-space discrepancy (including bi- maxillary protrusion and severe crowding in maxilla and mandible) indicate premolar extractions, when the intervention should be done, and whether to extract the first or second premolar. Therefore, in this article we highlight the premolar exodontia considerations for orthodontic and orthognathic treatment planning (pre-treatment) via discussing the basic mechanics and advantages of intra-/inter-arch movements. This is followed by presenting clinical cases exhibiting the incorporation of premolar extractions in (a) pre-surgical orthodontic treatment; (b) surgical plan and intervention; and (c) post-surgical outcome and prognosis. Alternative techniques and treatment options useful in tackling skeletal and dental malocclusion, including lateral body and sub-apical osteotomy(ies), that might consider integrating first and second premolar extractions, are also presented, herein.