This review focuses on current knowledge of the epidemiology, prevention, and treatment of invasive pneumococcal (IPD) and meningococcal disease (IMD). IPD decreased significantly with the introduction of effective conjugate vaccines but is on the rise again. Effective antibiotic therapy of IPD includes the combination of a beta-lactam and a macrolide with additional considerations in meningitis. Steroids are mandatory in pneumococcal meningitis but not indicated in pneumococcal pneumonia except in the setting of refractory shock. There is increasing concern about the cardiovascular complications of IPD. IMD continues to be a significant health problem with major concerns about rising antibiotic resistance.