Nontuberculous mycobacterial pulmonary infections are increasingly recognized in patients with CF. This may reflect the increasing longevity of this population with increased environmental exposure time, a higher clinical index of suspicion, and/or some as yet unidentified predisposing factor(s). The most common species of NTM in CF is MAC, followed by M abscessus. We recommend that adult patients with CF be screened for the presence of nontuberculous mycobacteria in pulmonary secretions on a regular basis, and that consideration be given to this diagnosis if a patient has an escalating pattern of exacerbations or admissions. Positive cultures are likely to indicate disease if they are multiple or if a patient has clinical evidence of pulmonary disease exacerbation (increased cough, increased purulence of secretions, systemic manifestations such as fever, weight loss) that is not responding to conventional antibiotic therapy. Cystic fibrosis patients who do not respond to treatment for the usual organisms should be carefully re-evaluated for the presence of NTM and treated with a macrolide-containing multidrug regimen directed against the identified NTM if diagnostic criteria are met. Novel treatments with cytokines and intermittent dosing of antibiotics are currently under investigation in non-CF populations and may have applicability to CF in the future.