Nontuberculous mycobacteria (NTM) are found in approximately 10 % of cystic fibrosis (CF) patients, but only a portion will develop NTM disease. The management of CF lung disease should be optimized, including antibiotic therapy targeted to the individual's usual airway bacteria, prior to considering treatment for NTM lung disease. Those who meet criteria for NTM lung disease may not necessarily require treatment and could be monitored expectantly if symptoms and radiographic findings are minimal. However, the presence of Mycobacterium abscessus complex (MABSC), severe lung disease, and/or anticipated lung transplant should prompt NTM therapy initiation. For CF patients with Mycobacterium avium complex (MAC), recommended treatment includes triple antibiotic therapy with a macrolide, rifampin, and ethambutol. Azithromycin is generally our preferred macrolide in CF as it is better tolerated and has fewer drug-drug interactions. MABSC treatment is more complex and requires an induction phase (oral macrolide and two IV agents including amikacin) as well as a maintenance phase (nebulized amikacin and two to three oral antibiotics including a macrolide). The induction phase may range from one to three months (depending on infection severity, treatment response, and medication tolerability). For both MAC and MABSC, treatment duration is extended 1-year post-culture conversion. However, in patients who do not achieve culture negative status but tolerate therapy, we consider ongoing treatment for mycobacterial suppression and prevention of disease progression.