For over a century, canines have been used to study adaptation to surgical lung resection or pneumonectomy (PNX) that results in a quantifiable and reproducible loss of lung units. As reviewed by Schilling (1965), the first successful experimental pneumonectomies were performed in dogs and rabbits in 1881. By the early 1920s, it was appreciated that dogs can function normally with one remaining lung that increases in volume to fill the thoracic cavity (Andrus, 1923; Heuer and Andrus, 1922; Heuer and Dunn, 1920); these pioneering observations paved the way for surgeons to perform major lung resection in patients. Reports in the 1950s (Schilling et al., 1956) detail surprisingly well-preserved work performance in dogs following staged resection of up to 70% of lung mass. Since then, the bulk of the literature on post-PNX adaptation has shifted to rodents, especially for defining molecular mediators of compensatory lung growth. Because rodents are smaller and easier to handle, more animals can be studied over a shorter duration, resulting in time and cost savings. On the other hand, key aspects of lung anatomy, development, and time course of response in the rodent do not mimic those in the human subject, and few rodent studies have related structural adaptation to functional consequences. In larger mammals, anatomical lung development more closely resembles that in humans, and physiological function can be readily measured. Because dogs are natural athletes, functional limits of compensation can be characterized relatively easily by stressing oxygen transport at peak exercise. Thus, the canine model remains useful for relating structure to function, defining sources and limits of adaptation as well as evaluating therapeutic manipulation. This chapter summarizes key concepts of compensatory lung growth that have been consolidated from canine studies: (i) structure-function relationships during adaptation, (ii) dysanaptic (unequal) nature of compensation, and (iii) signals for initiation of cellular growth.