Streptococcus pneumoniae (pneumococcus) remains a common cause of disease and death throughout the world. Despite considerable research into various aspects of this infection, there still remain a number of unresolved issues, as well as considerable ongoing controversies, particularly with regard to its optimal management. Among the risk factors for pneumococcal pneumonia, cigarette smoking has been shown to play a major role, more recently among HIV-infected individuals. Considerable recent research has focused on determining the role of the various protein virulence factors in disease pathogenesis. Among the ongoing controversies has been an appreciation of the true impact of antimicrobial resistance on the outcome of pneumococcal infections, as well an understanding of the role of combination antibiotic therapy in the more severely ill hospitalized cases. An important advance in the prevention of pneumococcal infections has been the introduction of the pneumococcal protein conjugate vaccine.