Computational modeling has become fundamental to the advancement of biology and medicine. Digital computers now make high-fidelity models of virtually unlimited complexity possible. However, as George Box cautioned, “All models are wrong, but some are useful”, which implies that the ultimate usefulness of a model manifests when it is replaced by an even more useful one. Future models will become increasingly complex, exhibiting new emergent behaviors that reflect multi-scale structure and function in biologic systems. Future models, perhaps aided by machine learning, will also become increasingly personalized, facilitating patient-specific disease management. We can thus expect computational modeling to continue to advance the science of lung pathophysiology and the practice of clinical pulmonary medicine.