Large chest wall defects, as a result of wide local excision of chest wall pathology, require skeletal and soft-tissue reconstruction to restore the anatomical shape, structure, and respiratory function of the thorax. Reconstruction is challenging and requires the surgical reconstructive team to understand the anatomic and physiologic morbidity related to the defect and the choice of reconstructive techniques available to restore form and function. Rapidly emerging 3-dimensional (3D) printing technology allows the reconstructive surgical team to customize the therapeutic process of skeletal reconstruction by accurately mimicking the shape and structure of the chest wall being replaced. An integrated knowledge of the anatomy, physiology, mechanics of breathing, and respiratory tests is important to restore form and function. The focus of this article is to review the anatomy, physiology, and assessment of respiratory function from the classical textbooks and integrate this knowledge with the precise anatomy of the chest wall created by 3D printing technology. By doing so, this article will demonstrate how 3D printing may help the reconstructive team to understand the anatomic and physiologic morbidity related to the chest wall defect and the importance of taking each of these aspects into consideration when undertaking chest wall reconstruction of the thorax.