BACKGROUND: Epidemiological and other studies suggest that a diet rich in omega-3 essential fatty acids (derived from fish oil) may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis (CF). OBJECTIVES: To determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality. To identify any adverse events associated with omega-3 polyunsaturated fatty acid supplementation. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Authors and persons interested in the subject of the review were contacted.Most recent search: April 2007 SELECTION CRITERIA: Randomised controlled trials in people with CF comparing omega-3 fatty acid supplements with placebo. DATA COLLECTION AND ANALYSIS: Two authors independently selected the studies for inclusion in the review, independently extracted data and assessed the methodological quality of the studies. MAIN RESULTS: Searches identified seven studies; three of which, involving 48 participants, were eligible for inclusion in the review. Two studies compared omega-3 fatty acids to olive oil controls for a six-week treatment period. One study compared omega-3 fatty acids in the form of a liquid dietary supplement containing polyunsaturated fatty acids to a liquid dietary supplement control for six months. One short-term study (19 participants) comparing omega-3 to placebo reported a significant improvement in forced expiratory volume in one second, forced vital capacity and Shwachman score and a reduction in sputum volume in the omega-3 group. The longer-term study (17 participants) demonstrated a significant increase in essential fatty acid content in neutrophil membranes in study participants taking omega-3 supplements compared to placebo, weighted mean difference 0.90 (95% confidence interval 0.46 to 1.34). AUTHORS' CONCLUSIONS: This review found that regular omega-3 supplements may provide some benefits for people with CF with relatively few adverse effects, although the evidence is insufficient to draw firm conclusions or to recommend routine use of supplements of omega-3 fatty acids in people with CF. This review has highlighted the lack of data for many of the outcomes likely to be meaningful to people with or making treatment decisions about CF. A large, long-term, multicentre, randomised controlled study is needed in order to determine if there is a significant therapeutic effect and to assess the influence of disease severity, dosage and duration of treatment. Future researchers should note the need for additional pancreatic enzymes.