Cystic fibrosis (CF) is the most common autosomal recessive disease among Caucasians. It is due to a mutation in the cftr gene, which encodes the CF transmembrane conductance regulator (CFTR), a chloride channel located in the plasma membrane of mucus-secreting epithelial cells. Numerous other functions of the CFTR protein were identified recently. The survival gains achieved in CF patients over the last 30 years have led to the emergence of delayed complications, one of which is bone disease. The fracture risk is increased from late adolescence onward. Vertebral fractures have an estimated prevalence of 14% among CF patients and can cause severe respiratory complications. Bone mineral density (BMD) is below the age-specific range. Among young adults with CF, 23.5% have BMD values below the cutoff for osteoporosis. Z-scores, which are decreased in children with CF compared to healthy controls, diminish further in adolescence as a result of inadequate peak bone mass accumulation. Studies have shown increased bone resorption, most notably during infectious episodes, and disturbances in bone formation. The numerous pathophysiological mechanisms that contribute to diminish bone strength in CF patients include exocrine pancreatic failure with malabsorption, protein-calorie malnutrition, inflammation related to recurrent infection, and deficiencies in vitamins D and K. In addition, many recent studies support a role for abnormal CFTR function in the osteoblast dysfunction seen in CF. Appropriate diagnostic and therapeutic management of osteoporosis in CF patients is crucial. Risk factors for osteoporosis should be corrected to the extent possible. Oral bisphosphonate therapy may deserve consideration, particularly in adults.