Pneumococcal meningitis is a common infection in adults for which penicillin has long been the drug of choice. Optimal treatment has recently become controversial, however, owing to an alarming increase in the number of penicillin-resistant isolates. The authors report a representative case of meningitis caused by such an organism, and provide a discussion of the history, mechanisms of resistance, laboratory evaluation, and treatment of these infections. Guidelines for prevention are also reviewed, including a renewed call for utilization of the 23-valent pneumococcal vaccine.