Thirteen bacteremias and 25 nonbacteremic infections caused by Pseudomonas spp. occurred in 22 of 236 children with human immunodeficiency virus infection with a rate of infection of 0.098 (bacteremia, 0.030) per patient year. Four patients were neutropenic (less than 500/microliters). Central venous catheter (CVC)-related infections were most frequent (n = 20) followed by otitis externa (n = 6) and pneumonia (n = 5). Pseudomonas aeruginosa was the most common isolate and caused both CVC-related and CVC-unrelated infections, whereas other Pseudomonas spp. and Xanthomonas maltophilia were almost exclusively associated with CVC-related infections. The children who received appropriate therapy had a favorable outcome. In 7 CVC-related infections (35%) the catheter was removed. Pseudomonas spp. are of increasing importance in human immunodeficiency virus-infected children causing significant morbidity and increased hospitalization. These infections may be life-threatening if appropriate therapy is not vigorously initiated.