Barrett's esophagus (BE) is a premalignant condition, and a recognized complication of severe gastroesophageal (GE) reflux. Children with cystic fibrosis (CF) have a marked predilection to develop GE reflux, but Barrett's esophagus is one complication of GE reflux not previously described in CF. We describe in detail two adolescents with CF who were found to have Barrett's esophagus, and mention three other cases. The presence of Barrett's esophagus in CF patients may be missed because GE reflux is often relatively silent in CF, because patients may consider mild upper gastrointestinal (GI) symptoms as "part of CF," and because of the nature of Barrett's epithelium itself. Upper gastrointestinal (GI) endoscopy with documentation of landmarks and multiple targeted biopsies should be performed in children with CF with even mild symptoms of GE reflux or an abnormal 24 h intra-esophageal pH study. Any biopsies containing columnar epithelium should be stained with Alcian blue at pH 2.5 to look for goblet cell metaplasia, i.e., Barrett's esophagus. Children with CF may be a high-risk group for development of Barrett's esophagus and its complications, especially given the increased survival in CF.