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Haemophilus influenzae type b (Hib) conjugate vaccines have proved extremely efficacious in healthy children. True Hib vaccine failures are rare. Hib conjugate vaccines were introduced for routine immunization in the United Kingdom and the Republic of Ireland in 1992. Coincident with this, active prospective and national surveillance via pediatricians, microbiologists, and public health physicians was commenced to assess the clinical and immunological factors associated with vaccine failure. During the 6 years of the study, 115 children with true vaccine failure were reported. Of the children who were vaccinated before 12 months of age, a clinical risk factor was detected in 20%, an immunological deficiency was detected in 30%, and one or both were detected in 44%. Children who were vaccinated after 12 months of age were more likely to have one or both factors (67%). Thirty percent (33 of 105) of children with true vaccine failure had a low Hib antibody response (concentration, !1.0 mg/mL) after disease, but the majority then responded to a further dose of Hib vaccine. Children who develop Hib disease despite vaccination deserve further clinical and immunological evaluation. The first vaccine to be developed against Haemophilus influenzae type b (Hib) was composed of polyribosylribitol phosphate (PRP), the organism’s capsular polysaccharide. An early trial of this vaccine demonstrated 190% efficacy in children who received vaccine when they were >18 months of age, but it provided no protection in younger children [1]. The conjugation of PRP to protein has lead to the development of Hib vaccines with enhanced immunogenicity in infants and the ability to induce immunological memory. The subsequent implementation of these vaccines has resulted in dramatic reductions in the rate of Hib disease [2].