Stenotrophomonas maltophilia is a ubiquitous organism associated with opportunistic infections. In the immunocompromised host, increasing prevalence and severity of illness is observed, particularly opportunistic bloodstream infections and pneumonia syndromes. In this article, the classification and microbiology are outlined, together with clinical presentation, outcomes and management of infections due to S. maltophilia. Although virulence mechanisms and the genetic basis of antibiotic resistance have been identified, a role for standardized and uniform reporting of antibiotic sensitivity is not defined. Infections due to S. maltophilia have traditionally been treated with trimethoprim-sulfamethoxazole, ticarcillin-clavulanic acid, or fluoroquinolone agents. The use of combination therapies, newer fluoroquinolone agents and tetracycline derivatives is discussed. Finally, measures to prevent transmission of S. maltophilia within healthcare facilities are reported, especially in at-risk patient populations.