Despite the availability of safe and effective hepatitis B virus (HBV) vaccines for >20 years, strategies targeting risk groups failed to sufficiently control hepatitis B disease at the population level; this is mainly because of difficulties in risk identification and in program implementation. Hence, the global burden of disease of HBV still is substantial. The World Health Organization recommends universal vaccination against hepatitis B to ultimately eliminate HBV; this recommendation had been progressively implemented to reach 168 countries with a universal program by the end of 2006. However, hepatitis B immunization is currently becoming endangered of losing its place on the agendas of governments, agencies, and international organizations, mainly because of the increasing success of these immunization programs and the interest in newer vaccine-preventable diseases and the related programs.This publication aims to show that vaccination programs targeting newborns and infants are preferable to achieve this goal. The benefits of universal HBV vaccination for newborns and infants are: higher impact on chronic carrier rate and transmission; established potential of high vaccine coverage in this age group; opportunities to combine HBV vaccination with existing universal vaccination programs for newborns and infants; and impact on perinatal transmission, if vaccination is started shortly after birth. Moreover, the safety, immunogenicity, and long-term efficacy of newborn and infant HBV vaccination have been proven extensively. In summary, newborn and infant HBV vaccination programs should be considered the preferred strategy, capable of providing important and sustained impact on global HBV incidence, even if they have a delayed impact on sexual transmission of HBV.