The incidence of NTM pulmonary infections increasingly is recognized in patients with CF. This may reflect the increasing longevity of this population with increased environmental exposure time, a high index of suspicion, and/or some as of yet unidentified predisposing factor(s). The most common species of NTM in CF is MAC, followed by M. abscessus. The authors recommend that adult patients with CF be screened for the presence of NTM pulmonary secretions on a regular basis. 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, or systemic manifestations such as fever and weight loss) that is not responding to conventional antibiotic therapy. CF patients who do not respond to treatment for the usual organisms should be re-evaluated for the presence of NTM and treated with a macrolide-containing regimen directed against the identified NTM if diagnostic criteria are met. Novel treatments with cytokines and intermittent dosing of antibiotics are currently under investigation.