Nontypeable Haemophilus influenzae has emerged as an important human pathogen and is associated with a wide range of diseases. As methods for subtyping isolates have improved, our understanding of the epidemiology and pathogenesis of nontypeable H. influenzae disease has grown. These advances have facilitated identification of a number of bacterial factors with potential as vaccine components. In this review we discuss methods of classifying nontypeable H. influenzae, the epidemiology of disease due to these organisms, bacterial and host factors contributing to disease pathogenesis, and the status of efforts to develop an effective vaccine.