Streptomyces are saprophytic soil organisms rarely known to cause invasive infections other than mycetoma. We report 6 cases of invasive Streptomyces infections and review 13 previously reported cases. Our series included 2 cases of lung abscess or pneumonitis, 3 cases of central venous catheter–related bloodstream infection, and 1 case of possible hypersensitivity pneumonitis. Most previous cases also included lung infections and bloodstream infections. Preexisting conditions, such as cancer, AIDS or HIV infection, presence of a central venous catheter, and prosthetic heart valve, were present in all cases since 1985. Diverse Streptomyces species were involved, consistent with the highly opportunistic nature of the infections. Clinical management depended on the clinical situation of individual cases without consensus. Available susceptibility data showed that Streptomyces organisms were consistently susceptible to amikacin; frequently susceptible to imipenem, clarithromycin or erythromycin, minocycline, and trimethoprim-sulfamethoxazole; and infrequently susceptible to ciprofloxacin and ampicillin. The diagnosis of Streptomyces infection required microbiologic and pathologic correlation to rule out contamination.