Respiratory disease in cystic fibrosis (CF) patients is characterized by purulent secretions in the airways, recurrent respiratory infections and progressive deterioration of lung function. Sputum from CF patients has a high concentration of DNA which is released by dead leukocytes. DNA is a contributor to the viscoelastic properties of sputum. Recombinant human DNase has been shown to decrease the viscoelastic properties of respiratory secretions of patients with CF in vitro. This article outlines the phase 1, 2 and 3 trial of rhDNase that have been performed in the UK and in the US. The largest of these trials, the phase 3 trial, involved 968 patients over a 24 week period. There was improvement in FEV1 by 6% in the patients receiving rhDNase. Compared to placebo controlled patients, patients given aerosolized rhDNase spent 1.2-1.4 less days in hospital and had 2.4-2.7 fewer days of antibiotic treatment. There was no evidence of an asthmatic response. There was an increased incidence of voice alteration in the rhDNase groups (16% and 12% compared to 7%). An antibody response was seen in up to 5% in the rhDNase patients over the 24 week period, although this appeared to be without any clinical effect. In conclusion, the clinical trials of aerosolized rhDNase show that it appears safe, improves spirometry, and reduces the need for antibiotic treatment for acute exacerbations of the pulmonary disease of CF.