Haemophilus influenzae is a major pathogen in acute otitis media (AOM) causing disease that is not clinically distinguishable from that caused by Streptococcus pneumoniae. AOM caused by H. influenzae is particularly associated with older age and recurrent disease. Antibiotics differ in their ability to eradicate H. influenzae from the middle ear space. In the United States, widespread pneumococcal vaccination has increased the importance of H. influenzae as a major therapeutic challenge in the treatment of AOM.