The paper reviews the literature on the epidemiology of Hib disease and the effectiveness of Hib conjugate vaccine (HibCV) in HIV-infected children. The current three-dose primary Hib conjugate vaccine schedule in low-income settings has had a striking impact on the incidence of Hib disease. However, HIV-infected children have an almost 6-fold higher risk of Haemophilus influenzae type b (Hib) invasive disease than HIV-uninfected children and HibCV effectiveness is lower in this population. HIV-related HibCV failures are difficult to detect without well functioning surveillance systems and HIV testing of cases. Breakthrough Hib cases have been noted in vaccinated HIV-infected children in South Africa. A HibCV booster dose in addition to the three-dose primary schedule is routine in many, but not all, high-income countries. In order to determine whether a booster dose should be given to HIV-infected children in developing countries, well-designed studies need to be conducted to better determine the persistence of protective antibody concentrations, response to booster doses of vaccine as well as timing of and risk factors for vaccine failure in HIV-infected children both treated and naive to antiretroviral drug therapy (ART). Meanwhile, physicians and public health personnel should be especially vigilant at ensuring that HIV-infected infants receive their primary doses of HibCV, ART and co-trimoxazole prophylaxis. Until more definitive evidence is available, physicians may also need to consider a booster dose for such children irrespective of ART status. In any updating of vaccine schedules, HIV-infected children need particular consideration.