Chronic granulomatous disease is a rare inherited disorder of phagocytic cells which results in a susceptibility to infections of catalase-positive bacteria and fungi (especially Aspergillus species), as well as granuloma formation. The mainstay of therapy is antibacterial and antifungal prophylaxis. Trimethoprim sulfamethoxazole is the drug of choice for the prevention of bacterial infection, while itraconazole is most widely used for the prevention of fungal infection. Immunomodulatory agents, such as IFN-phi, have a role in the prevention and treatment of intractable infection. New antifungal agents provide the promise of improved cure rates for invasive Aspergillus, while bone marrow transplants and gene therapy may offer the promise of complete cure.