Streptococcus pneumoniae is the leading cause of bacterial meningitis in the United States and accounts for significant morbidity and mortality in essentially all age groups. Prompt recognition and treatment can improve outcomes. In this clinical article, Dr. Jeffrey A Rumbaugh, from the Division of Neuro-Infectious Disease at Johns Hopkins University, reviews the clinical manifestations of S pneumoniae infection, with emphasis on neurologic symptoms and key features that can help avoid pitfalls leading to missed or late diagnosis. Current diagnostic laboratory techniques are evaluated, and up-to-date treatment recommendations, based on the most recent research and expert opinion are incorporated. Recent research regarding the importance of endocarditis and bacteremia to neuropathogenesis as well as the effect of bacterial meningitis on neurogenesis is presented.