Chronic pulmonary infection is one of the hallmarks of lung disease in cystic fibrosis. Infections dominated by organisms of the Burkholderia cepacia complex, a group of at least 17 closely-related species of gram-negative bacteria, are particularly difficult to treat. These infections may be associated with a fulminant necrotising pneumonia, and are greatly feared by patients. Burkholderia cepacia bacteria are innately resistant to many common antibiotics and able to acquire resistance against many more. Since strict patient segregation was introduced to cystic fibrosis medical care, the incidence of the more virulent epidemic strains has fallen, and new infections are more likely to be with environmentally-acquired strains which seem to exhibit less virulence. Nonetheless, exacerbations of respiratory symptoms require effective therapy directed against the dominant bacterial species. Although evidence-based guidelines exist for the treatment of respiratory exacerbations involving Pseudomonas aeruginosa, the most common chronic infection in cystic fibrosis, these cannot be directly extended to Burkholderia cepacia complex infections. The aim of this review is to assess the available trial evidence for choice and application of treatments for Burkholderia cepacia complex infections.