An urgent need exists for vaccines to prevent infections caused by nontypeable Haemophilus influenzae and Moraxella catarrhalis. These bacteria cause otitis media in children, a clinical problem associated with enormous morbidity and cost. H. influenzae and M. catarrhalis also cause lower respiratory tract infections in adults with chronic lung disease. Infections in this clinical setting are associated with disability and death. Recent progress in identifying potential vaccine antigens in both bacteria raises great promise in developing effective vaccines. This paper reviews the key issues in vaccine development for H. influenzae and M. catarrhalis, including areas where progress has been stalled, and proposes areas that deserve investigation in the next 5 years.