Interstitial lung diseases (ILDs) continue to have high morbidity and mortality in part because many gaps remain in our understanding of the mechanistic basis of disease initiation and progression. These studies remain challenging in patients because of the inaccessibility of tissue samples during the early stages of disease. Animal and translational model systems provide valuable tools for use in discovering mechanisms of disease pathogenesis and in testing novel targets for therapeutic intervention. Here we review models which address the following areas known to be important for the development of ILD; disrupted cellular proteostasis, organellar dysfunction, DNA damage and cellular senescence, and the preclinical models used to understand these processes. We also review ILDs associated with occupational exposures, connective tissue diseases, and rare diffuse ILDs. Finally, we review both animal models and human cell-based models currently in use in preclinical studies.