Research indicates a high burden of pneumococcal disease and great potential benefits of conjugate vaccines in Indigenous Australian children, who should have high priority for delivery of these vaccines. Incidence of invasive pneumococcal disease in Indigenous people in central Australia is the highest reported in the world (2053 per 100,000 persons per year in those aged under two years). Acute respiratory infection is a major cause of morbidity in Indigenous children in rural and remote areas. Early pneumococcal colonisation of the nasopharynx and high rates of carriage are seen in Indigenous children, and are probably related to their high rates of ear disease. Current seven-valent conjugate vaccines are likely to cover about two-thirds of invasive isolates in Indigenous Australian children; 11-valent vaccines will cover a higher proportion. Questions remain about the best vaccine carrier protein and the likely impact of vaccine on ear disease, pneumococcal carriage and antibiotic resistance.