Stenotrophomonas maltophilia is a gram-negative bacillus that is increasingly associated with serious nosocomial infections, especially in immunocompromised patients; however, the occurrence of endocarditis due to this organism is rare. This report describes a case of S. maltophilia endocarditis associated with a central venous catheter. The literature on Stenotrophomonas endocarditis is reviewed. Given the high morbidity and mortality of these infections, early antibiotic therapy utilizing trimethoprim-sulfamethoxazole, along with a second agent and removal of prosthetic devices, is recommended.