With patients with cystic fibrosis (CF) living longer and reaching adulthood, conditions before not frequently encountered now play a larger role in the spectrum of CF related symptoms and complaints which continue to challenge clinicians in both outpatient and acute settings. It is in this context that the radiologist and different radiological imaging modalities can aid the clinician in order to establish an accurate diagnosis and steer appropriate treatment. In this chapter, we present a comprehensive review of common and not so common radiological features of both pulmonary and extra-pulmonary manifestations of CF. With a huge variety of scans available at one’s finger tips, or to be more precise, at the end of an electronic request form, it is vital that clinicians are familiar with the different existing imaging modalities, what information to expect from each one of them and the most appropriate scan to request to answer the specific clinical question, taking into consideration the patient’s characteristics and needs- in other words, how to make best use of their Radiology Department. In this way, the required information can be obtained most rapidly and efficiently by using the correct test or tests performed in the correct order. Chest radiographs are usually the exam of choice for the initial assessment and sequential follow-up of pulmonary disease in adult CF patients. It employs a very small dose of ionizing radiation and can be of great value in the detection of new infiltrates in acute infective exacerbations or diagnosing complications such as a pneumothorax. Plain radiography is also much used in patients complaining of acute abdominal pain, although findings can be non-specific and patients may require further imaging to characterize the abdominal pathology. An abdominal radiograph delivers a higher radiation dose and therefore should not be performed unnecessarily. Barium studies are not commonly used and it is believed that barium may cause obstruction in CF patients due to the thick intraluminal secretions. On the other hand, hypertonic oral contrast is used in some patients for the treatment of distal intestinal obstructive disease (DIOS). Air and contrast enemas continue to be used for the reduction of intussusception. Ultrasound imaging does not carry any radiation hazard and has the added advantage of being relatively cheap and readily available. It can be useful in the chest in the assessment of pleural effusion or collection, but is most valuable for the evaluation of abdominal organs (e.g. liver, gallbladder, kidneys, spleen) and in patients with acute abdominal pain or suspected bowel pathology, such as DIOS, appendicitis or intussusception. The disadvantage of this modality is that it is completely operator dependent and sometimes images obtained are suboptimal due to patient related factors, such as obesity or overlying distended bowel gas.