Stenotrophomonas maltophilia is an emerging multidrug-resistant global opportunistic pathogen. The increasing incidence of nosocomial and community-acquired S. maltophilia infections is of particular concern for immunocompromised individuals, as this bacterial pathogen is associated with a significant fatality/case ratio. S. maltophilia is an environmental bacterium found in aqueous habitats, including plant rhizospheres, animals, foods, and water sources. Infections of S. maltophilia can occur in a range of organs and tissues; the organism is commonly found in respiratory tract infections. This review summarizes the current literature and presents S. maltophilia as an organism with various molecular mechanisms used for colonization and infection. S. maltophilia can be recovered from polymicrobial infections, most notably from the respiratory tract of cystic fibrosis patients, as a cocolonizer with Pseudomonas aeruginosa. Recent evidence of cell-cell communication between these pathogens has implications for the development of novel pharmacological therapies. Animal models of S. maltophilia infection have provided useful information about the type of host immune response induced by this opportunistic pathogen. Current and emerging treatments for patients infected with S. maltophilia are discussed.