Australian Aboriginal children experience the highest rates of bacterial respiratory diseases reported in the literature. Neonatal acquisition of multiple bacterial pathogenic species and strains predicts persistent and severe disease throughout childhood, particularly infective ear disease. The dynamics of bacterial nasopharyngeal colonization and transmission are poorly understood. The importance of host factors, bacterial competition and co-operation in the transition from asymptomatic carriage to disease are also uncertain. Treatment outcomes are poor, possibly due to the high density of bacterial infection following early age exposure, poor compliance and increasing levels of antibiotic resistance. The relationship between antibiotic use, clinical outcomes and bacterial resistance needs to be better understood in high-risk populations if the benefits associated with treatment are to be maximized. While there is an urgent need for vaccines, the early age of infection and the high rates of transmission and bacterial antigenic diversity mean these may also be less effective than predicted from studies in low-risk populations.