Stenotrophomonas maltophilia is emerging as an important opportunistic pathogen in nonimmunocompromised hosts. It has been widely described that bacteremia and ventilator-associated pneumonia due to S. maltophilia cause significant mortality and morbidity. However, a recent study suggests that a positive respiratory isolate in the absence of consolidation does not require specific therapy. Antimicrobial resistance among S. maltophilia strains is an escalating problem with significant consequences on morbidity, mortality and healthcare costs. Although trimethoprim-sulfamethoxazole (TMP-SMX) continues as the preferred agent, the marked multiresistance evidenced by some species, prompts the need to develop new antimicrobial agents and search for synergistic combinations. New fluoroquinolones seem to be an encouraging option for treatment and may become very useful in the treatment of severe infections due to S. maltophilia. Much remains to be understood of the epidemiology of S. maltophilia and more information on nosocomial reservoirs and routes of transmission of the bacterium is needed. Appropriate antimicrobial selection, surveillance systems, and effective infection-control procedures must be addressed to limit antimicrobial resistance and restrict the spread of this organism.