Actinobacillus actinomycetemcomitans is a small fastidious gram-negative coccobacillus that fails to grow on MacConkey's agar. Slow growth in broth may lead to delays in diagnosis. First described in 1912, A. actinomycetemcomitans has been recognized since 1962 as capable of causing serious infections in humans. Such infections include periodontal infection, soft tissue abscess (often in association with Actinomyces species), and systemic infection, most commonly endocarditis. Fifteen cases and a review of the English-language literature are presented to define the epidemiology and clinical features of infection due to A. actinomycetemcomitans. Therapy for infection due to A. actinomycetemcomitans has most commonly involved ampicillin or penicillin, often in conjunction with an aminoglycoside. However, resistance to penicillin or ampicillin is common. Antimicrobial agents with a high degree of in vitro activity included cefazolin, cefotaxime, cetriaxone, aminoglycosides, and chloramphenicol. Therapy should be guided by clinical response and in vitro susceptibility testing.