Chronic infection and inflammation are the hallmarks of cystic fibrosis lung disease. As cystic fibrosis patients are living longer owing to more intense treatment, multidrug-resistant organisms are being isolated increasingly from patients' respiratory tracts. While the adverse effects of Pseudomonas aeruginosa and Burkholderia cepacia complex are well described, less is known about the clinical significance of other emerging multidrug-resistant organisms, such as methicillin-resistant Staphylococcus aureus and Stenotrophomonas maltophilia. Owing to multiple mechanisms of antimicrobial resistance, these organisms are difficult to treat and often require combination antibiotic therapy. Until more is known about their pathogenicity and effect on clinical outcomes, physicians should be aware of the potential transmissibility of these organisms and implement adequate infection control strategies.