Clinical trials for the treatment of cystic fibrosis (CF) lung disease are important to test and optimize new therapeutic interventions. To evaluate the effect of these interventions, sensitive and accurate outcome measures are needed. The most commonly used endpoints are spirometric variables such as the forced expiratory volume in one second (FEV1) and respiratory tract exacerbations (RTE). Unfortunately, these endpoints are relatively insensitive to monitor progression of CF lung disease, and thus require a large number of patients when used in clinical studies. In addition, these endpoints are not suitable to study CF lung disease in young children. Chest computed tomography (CT) holds great promise for use as a sensitive surrogate endpoint in CF. A large body of evidence has been produced to validate the use of chest CT as primary endpoint to study CF lung disease. However, before chest CT can be used in clinical trials, it has to be recognized as a validated surrogate endpoint by regulatory agencies. The aim of this review is to summarize what is currently known about the use of chest CT as surrogate endpoint in clinical trials in CF.