Pneumococcal pneumonia poses a serious threat to children in developing countries and remains an important disease in the industrialized world. Capsular polysaccharide is the only bacterial factor proven to contribute to pathogenesis. However, the mechanisms responsible for the hypoxemia, toxemia, crisis, and death associated with this common infection are poorly understood. Toxins secreted by the bacteria, byproducts of bacterial breakdown (e.g., pneumolysin or teichoic acid), or constituents of the intense inflammatory response in the lung might play a role in these phenomena. Malnourished children presumably carry less metabolic reserve with which they can resist the exceptional stresses of pneumococcal disease, and underlying parasitic infestation or other chronic infections, through release of potent mediators such as tumor necrosis factor or platelet-activating factor, might prime the mechanisms of host defense for a more fulminant and systemic response to infection. Vaccines that can protect infants are badly needed, and a better understanding must be gained of the mechanisms by which this pathogen continues to cause such devastating disease in the world's children and elderly.