Although most species in the genus Burkholderia are not pathogenic for healthy persons, a few are capable of causing severe, life threatening infection. B. mallei and B. pseudomallei are the causative agents of glanders and melioidosis, respectively. Interest in these species has increased recently owing to their potential for use as agents of bioterrorism. B. cepacia emerged during the past two decades as an important opportunistic pathogen among persons with certain underlying diseases. Persons with chronic granulomatous disease, a primary immunodeficiency, or cystic fibrosis (CF), the most common lethal inherited disorder in Caucasians, are at particular risk. In CF, respiratory tract infection may be chronic or associated with a rapid deterioration in pulmonary function. Studies in the early 1990s utilized a variety of genotyping techniques to provide compelling evidence of person-to-person transmission of B. cepacia among CF patients. This prompted the institution of rigorous infection control measures that have placed a heavy burden on persons with CF. More recent work has demonstrated that several distinct bacterial species actually exist among bacteria previously identified merely as B. cepacia. How these species, collectively referred to as the B. cepacia complex, differ with respect to their epidemiology, natural history, and pathology in CF is the subject of ongoing investigation.