Nontypeable Haemophilus influenzae (NTHI), a gram-negative bacterium that is considered an important human pathogen, causes a broad spectrum of disease in both adults and children. An effective vaccine against NTHI would reduce the incidence of disease and reduce the dependency on antibiotic therapies as a means of defense. The results from immunization studies with whole killed-cell formulations of NTHI indicate that it is feasible to protect against NTHI infections by vaccination. The limitation of a whole-cell formulation is the considerable strain-heterogeneity in NTHI strains. Several proteins on the outer membrane appear highly conserved and offer potential as vaccine candidates.