The hepatobiliary manifestations of cystic fibrosis (CF) encompass a broad clinical spectrum, from mild steatosis, associated with poor nutrition, to multilobular cirrhosis and the complications of portal hypertension. The factor(s) responsible for the development and progression of liver disease in a subset of patients with CF are unknown. Liver disease can be silent and progressive, manifesting only with complications associated with cirrhosis and portal hypertension. Clinical evaluation for detecting and monitoring the progression of liver disease includes the following: physical examination of the liver, biochemical tests of liver function and injury, and radiological imaging with abdominal ultrasonography. Careful monitoring should take place in all patients with CF, as currently, there are no sensitive and/or specific historical or biochemical markers to predict who is at risk for the development of liver disease. Current treatment options for CF-associated liver disease are very limited. The bile acid ursodeoxycholic acid may improve biochemical parameters of liver disease, but its long-term efficacy in preventing the progression of liver disease in CF is unproven. Treatment therefore rests on optimizing nutritional status; correcting fat-soluble vitamin, essential fatty acid, and other mineral deficiencies; and treating complications of end-stage liver disease, such as pruritus, ascites, and portal hypertension.