Controlled trials of antimicrobial chemotherapy for legionnaires' disease have not been performed, although erythromycin and tetracycline appear to be effective therapies. Laboratory data indicate that the activities of the fluoroquinolone and newer macrolide/azalide agents against Legionella pneumophila are superior to that of erythromycin, and case reports substantiate that the activities of these agents are at least equal. Results of clinical treatment with and laboratory testing of macrolides, tetracyclines, co-trimoxazole, chloramphenicol, aminoglycosides, fluoroquinolones, beta-lactam agents, and streptogramins are reviewed. The drugs of choice for the treatment of legionnaires' disease in immunocompromised or severely ill patients should be one of the fluoroquinolone antimicrobials rather than erythromycin.