Pseudomonas maltophilia (Xanthomonas maltophilia) is a frequently isolated commensal that is gaining increasing recognition as an opportunistic pathogen in debilitated hosts. We report three unusual infections due to P maltophilia that illustrate the ability of the organism to cause life-threatening illness. We describe a case of postoperative meningitis, a case of recurrent bacteremia complicated by ecthyma gangrenosum, and a case of native valve endocarditis in a drug addict. Because of frequent isolation from noninfected sites, the pathogenic potential of P maltophilia may be overlooked. The notable resistance of this organism is commonly used beta-lactam and aminoglycoside antibiotics may complicate therapy.