Detecting diffuse lung infiltrates on chest radiography is a common clinical problem. Many diverse pathological processes can cause diffuse lung disease. The presentation of these diseases can vary from acute to chronic and includes a wide array of radiological patterns that are optimally evaluated on high-resolution computed tomography of the chest. In diagnosing diffuse lung disease, it is helpful to focus on a few pivotal parameters to narrow the broad differential diagnosis. We describe the diagnostic approach to a patient with diffuse lung disease using the following key parameters: tempo of the pathological process, characteristics of the radiological pattern, and clinical context.