New insight has been gained into the mechanisms underlying the tissue tropism and inflammation of pneumococcal infection. Virulence has been linked to a transparent colonial morphology. Adherence has been characterized at the molecular level, and the importance of receptors arising upon activation of eukaryotic cells in promoting the progression to disease has been established. The contribution of peptidoglycan and teichoic acid to the generation of inflammation has suggested the need to couple anti-inflammatory therapy with antibiotic treatment in order to improve the outcome of invasive disease. Elucidation of the pathogenesis of pneumococcal infection, including the identification of virulence determinants by recently developed genetic strategies, can provide a paradigm for new mechanisms that are active in gram-positive bacterial infections and that are clearly distinct from the familiar pathways triggered by endotoxin.