Streptococcus pneumoniae continues to be the most common organism causing acute otitis media and sinusitis in infants and children and remains an important bacterial cause of pneumonia, septic arthritis, and bacterial meningitis in the pediatric age group. The definition, incidence, and mechanisms for penicillin resistance in pneumococcus are reviewed here. Physicians caring for children should know and understand these important concepts. At present, for most respiratory infections in children penicillin-resistant pneumococcus does not represent a clinical dilemma as far as regarding alteration of empiric antibiotic therapy. However, as this problem continues to grow, especially for patients with recurrent otitis media or sinusitis, physicians will be facing upper respiratory infections that are more commonly caused by these isolates and the antibiotic management of infections in the respiratory tract caused by penicillin and other antibiotic-resistant pneumococcal isolates will require modification.