Diffuse (interstitial) lung disease comprises a wide variety of relatively uncommon conditions, which present with characteristic clusters of clinical features and often with aberrant lung function. These diseases cause major morbidity and mortality due to lung injury and fibrosis. Some of these diseases are of known aetiology, whereas others are not. It has been suggested that the environment is a major contributing factor in this group of diseases. However, since not all individuals exposed to a common environment develop interstitial diseases, we can hypothesize that there is a genetic predisposition to their development. Therefore, if we can identify individuals who are genetically predisposed to develop diseases characterized by lung injury and fibrosis, then management strategies can be designed which will attempt to identify early disease and, in the longer term, to develop targeted genetic interventional approaches to treatment.