There area number of diseases that present with ground-glass opacification of the lung as a primary manifestation on chest radiography and thin-section computed tomography (CT). These diseases cannot be clearly categorized into the classic classification scheme of airspace and interstitial disease because there are features of both categories seen in the imaging and histologic findings. Ground-glass opacification has, therefore, been categorized as nonspecific by many radiologists. The fact that both the airspaces and interstitial tissues are often involved should have little importance when evaluating radiographs or high-resolution CT (HRCT) images. The role of the radiologist is evolving and is becoming more significant in the clinical evaluation of a patient presenting with so-called interstitial lung disease. In this article, an approach is described that hopefully will lead to an effective and narrow differential diagnosis when a radiologist is confronted with ground-glass opacification. The critical features in evaluating such cases include: (1) the duration of clinical symptoms; (2) the presence or absence of lung fibrosis, especially honeycombing; (3) the patient's history of smoking; and (4) the distribution of the disease. Each of these features is considered in this article in conjunction with the diseases that lead to ground-glass opacification. The recent thinking regarding nonspecific interstitial pneumonia and usual interstitial pneumonia also is discussed.