The development of vaccines against non-typeable Haemophilus influenzae and Moraxella catarrhalis represents a difficult challenge. Both bacteria are mucosal surface pathogens and protection may require a mucosal immune response. In addition, the surface antigens of non-typeable Haemophilus influenzae are hypervariable and animal models of infection with these bacteria may not be predictive of human efficacy. Vaccine development has focused on conserved surface exposed antigens, including integral outer membrane proteins, pili and other attachment factors, membrane-associated proteins, and lipooligosaccharide-protein conjugates. Several vaccine candidates are described that are antigenically conserved among strains, elicit biologically functional antibodies, and have efficacy in animal models.