Publisher Summary Haemophilus influenzae is a facultative anaerobe that has an absolute requirement for nicotene amide adenine and a source of haem. At the time, a gram-negative coccobacillus is frequently isolated from the sputum of individuals with influenzal pneumonia. The frequency of this observation led to the conclusion that this organism, named Haemophilus influenzae, is the cause of influenza. H. influenzae is more accurately defined as a commensal organism of the human respiratory tract, and it is shown to be a common cause of upper and lower respiratory tract infections. Occasionally, it also causes more serious, life-threatening invasive disease, such as meningitis. The pathogenesis of disease caused by nontypable H. influenzae and H. influenzae type b involves multiple steps. Although similar mechanisms are used to promote colonization of the nasopharynx, both organisms express unique virulence determinants that dictate the spectrum of disease they are able to cause. Although it is a major determinant of virulence, the capsule has played a useful role as the basis of the highly successful H. influenzae vaccine. In contrast, no such highly conserved virulence determinant is common to nontypable strains of H. influenzae, which complicates the search for a candidate vaccine for this group of organisms. As a consequence while disease due to type b stains is now rare, nontypable strains continue to be a significant cause of morbidity and often mortality in children.