Over the last 15 years, several clinical trials in subjects with cystic fibrosis (CF) have employed computed tomography (CT) scanning as an outcome surrogate. These research trials have increased our knowledge about the appearance of the lungs in patients with CF, and the relationship between the CT appearance, pulmonary function tests, and clinical outcomes. In addition, practical information has been gained on the use of CT scanning in CF research trials. In this article, practical issues on the use of CT scanning in CF clinical trials are presented and specific lessons from three of these trials are discussed.