High resolution computed tomography (CT) now has a central role in the evaluation of diffuse lung disease. It is of particular use in the formulation of a differential diagnosis. Whilst CT often conveys sufficient information to allow non-invasive diagnosis, it sometimes reveals atypical appearances, contributing to the continuing reclassification of diffuse lung disease and justifying histological evaluation in some patients. Thus, CT as a new technology does not always replace conventional diagnostic methods, but is best integrated with clinical assessment, other non-invasive investigations and surgical lung biopsy: this applies equally to clinical diagnosis and to the definition and reclassification of disease entities. In this article, we explore the optimal diagnostic use of CT. The limitations of CT series in simulating the clinical application of CT in the management of diffuse parenchymal lung disease highlight the need for an integrated approach to diagnosis, including corroborative data drawn from many sources. High-resolution computed tomography, when interpreted in the context of the pre-test probability, obviates invasive investigation in many cases. As descriptions of the CT appearances of individual diffuse lung diseases are refined, ongoing re-evaluation is required to establish which features can be regarded as pathognomonic, for diagnostic purposes, and how CT can be integrated into revised disease definitions so that the most clinically relevant diagnostic criteria are formulated.