We present a patient with cystic fibrosis who used nebulized levofloxacin off-label to suppress chronic Burkholderia cenocepacia pulmonary infection. The patient was initially using tobramycin inhalation powder (TIP) off-label continuously for suppression of chronic B. cenocepacia; this was changed to alternating months of nebulized levofloxacin and TIP. Following initiation of nebulized levofloxacin, the patient had significant improvement in respiratory symptom burden and lung function (as measured by forced expiratory volume in 1 second [FEV1]), and a decrease in the frequency of pulmonary exacerbations. Further research is necessary to determine whether the benefits observed with nebulized levofloxacin in our patient translate to a larger population of patients with chronic Burkholderia spp. pulmonary infection.