Acute pulmonary exacerbations (APE) are a complication of cystic fibrosis (CF) and are associated with morbidity and mortality. Methicillin‐resistant Staphylococcus aureus (MRSA) is one of many organisms that has been detected in the airways of patients with CF. This review provides an evidence‐based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti‐MRSA antibiotics (ie, ceftaroline, clindamycin, fluoroquinolone derivatives (ciprofloxacin, levofloxacin), glycopeptide derivatives (telavancin, vancomycin), linezolid, rifampin, sulfamethoxazole/trimethoprim (SMZ/TMP), and tetracycline derivatives (doxycycline, minocycline, tigecycline) in the treatment of APE and identifies areas where further study is warranted. A recent utilization study of antimicrobials for anti‐MRSA has shown some CF Foundation accredited care centers and affiliate programs are using doses higher than the FDA‐approved doses. Further studies are needed to determine the PK/PD properties in CF patients with clindamycin, minocycline, rifampin, SMZ/TMP, telavancin, and tigecycline; as well as, efficacy and tolerability studies with ciprofloxacin, clindamycin, doxycycline, levofloxacin, minocycline, rifampin, SMZ/TMP, in CF patients with MRSA.