A review of anaerobic bacteremia in the Neonatal Intensive Care Unit identified 29 episodes of clinically significant bacteremia occurring over the past 18 years. This experience suggested that certain clinical settings were associated with specific anaerobic infections. Although Gram-positive and Gram-negative anaerobes were isolated with similar frequency, 8 of 12 infants bacteremic within the first 48 hours of life were infected with Gram-positive, penicillin G-susceptible organisms whereas 11 of 17 infants older than 2 days were bacteremic with Gram-negative, penicillin G-resistant anaerobes. Eleven of 17 infants with anaerobic bacteremia associated with necrotizing enterocolitis were bacteremic with Gram-negative anaerobes. Five of 6 infants with anaerobic bacteremia associated with chorioamnionitis were bacteremic with Gram-positive anaerobes. These observations should be considered in making decisions regarding empiric therapy for the newborn at highest risk for anaerobic bacteremia.