Since 1990, there have been an increasing number of reports of nontuberculous mycobacteria (NTM) recovered from lower respiratory tract specimens of patients with cystic fibrosis (CF) lung disease. The eight reports from series of prospectively screened patients collectively note a prevalence of approximately 13%. Reasons for the increased reports in CF patients may be related to: (1) active searching for NTM; (2) complications of advancing survival length in which more pathogens are emerging; (3) improvements in culture technique that decrease bacterial overgrowth: (4) factors that favor transmission such as contaminated hospital water supplies; and (5) a more susceptible host reflecting increasing NTM infection in the general population. Distinguishing airway colonization by NTM from pathogenic NTM infection that contributes to the progression of the underlying CF lung disease can be particularly difficult. Treatment of NTM in CF can also be more difficult because: (1) altered drug absorption and metabolism, (2) pre-treatment polypharmacy including multiple antimicrobials, and (3) the susceptibility of other pathogens to some antimycobacterial agents confounding assessment of NTM treatment response.