Stenotrophomonas maltophilia can cause serious infections in immunocompromised patients. The aim of this systematic review was to establish what invasive infections in humans are caused by S. maltophilia and to evaluate the optimal choice of antibiotics for their treatment. MEDLINE, EBSCO, SCOPUS, SCINDEKS and GOOGLE SCHOLAR were systematically searched for clinical trials, observational studies, case reports or case series describing invasive infections with S. maltophilia in patients of any age. S. maltophilia may cause invasive infections of various tissues in hospitalized patients. In the great majority of cases it was susceptible to co-trimoxazole, levofloxacin and ceftazidime. In about three fourths of the cases, the treatment was successful, while less than 20% of the patients died. S. maltophilia is increasingly associated with serious invasive infections in hospitalized patients and due to growing trend of resistance to almost all antibiotics requires a careful approach to patients who is harboring this bacterium.