Gram-negative anaerobic bacteria belonging to the genera Bacteroides, Prevotella, and Porphyromonas represent the most common cause of endogenous, usually mixed, infections occurring after abdominal or gynecologic surgery. Anaerobes are important pathogens in oral-cavity infections as well as in systemic infections that originate from the mouth. Clinical interest in these organisms is linked to the therapeutic problems usually encountered in treating mixed infections. Despite their clinical relevance, very little is known about the pathogenetic mechanism of anaerobic infections. In Bacteroides species, the capsule has been thought to be important, and initially it was considered unique to Bacteroides fragilis, the most common pathogen. It has been claimed that the capsule is involved in adhesion, abscess formation, and impaired phagocytosis. However, other structures such as pili and extracellular substances, including metabolic by-products (e.g., short-chain fatty acids), have to be considered as potentially relevant pathogenetic mechanisms in anaerobic infections. Several extracellular enzymes have been investigated, but no clear evidence is available for establishing their relevance in disease mechanisms. Special attention should be devoted to enzymes able to digest IgA (IgA proteases), a first-line defense mechanism that is active in the mucosal membranes.