Haemophilus aphrophilus, an oral fastidious Gram-negative commensal with low pathogenicity, is a member of the HACEK group (H. aphrophilus, H. paraphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella spp.), and a rare cause of human infections. We reviewed the characteristics of 8 cases of H. aphrophilus infections diagnosed in our hospital from 1990-2003, and an additional 20 cases identified from the MEDLINE database, from 1990 to 2003. Their mean age was 47.4 years (range, 7-73 years), and 21 cases (75%) were male. The major manifestation was bone and joint infections (9 cases, 32%), including osteomyelitis, discitis, epidural abscess, spondylodiscitis, septic arthritis and prevertebral infection. Seven cases (25%) presented with infective endocarditis, involving native valves, and one underwent valvular replacement. Of note, 3 cases (10%) had ophthalmic infections (endophthalmitis in 2 cases and canaliculitis in 1), and 2 of them had previous ophthalmic procedures. Other manifestations included bacteremia, meningitis, brain abscess, cervical lymphadenitis, facial cellulitis, empyema, and purulent pericarditis and tamponade. All patients except 1 survived. Recent dental procedure was recalled by 11 cases (39%), and may be a predisposing factor for invasive H. aphrophilus infection. Appropriate antimicrobial therapy, such as a beta-lactam/beta-lactamase inhibitor, ceftriaxone or cefotaxime or a fluoroquinolone, can lead to a favorable clinical outcome.