Clinical trials in cystic fibrosis (CF) will continue to investigate a widening array of new therapeutics, ranging from gene therapy to antiinflammatory drugs and anti-infectives. A wide range of clinical trial endpoints is needed to adequately evaluate these agents. The existing "toolbox" of CF clinical trial endpoints includes pulmonary exacerbation rates, quality of life measures, growth, lung function, respiratory cultures, inflammatory markers, nasal potential difference, chest radiographs, chest computed tomography (CT), and newer imaging modalities. Clinical endpoints will be distinguished from surrogate endpoints; imaging is a surrogate endpoint. The qualities of an ideal outcome measure will be reviewed. The advantages and limitations of current endpoints will be identified, and the potential role for chest CT and newer imaging modalities discussed in this context. Finally, choosing appropriate endpoints for specific indications will be discussed.