Worldwide, Haemophilus influenzae type b (Hib) causes at least 3 million cases of severe disease each year. Approximately 400,000 children die annually due to pneumonia or meningitis caused by Hib [1]. Severe neurological sequelae occur in 15% to 30% of those who survive Hib meningitis [2]. Other, less frequent, manifestations of Hib are epiglottitis, septic arthritis, osteomyelitis, and septicemia [1–3]. Current polysaccharide–protein conjugate Hib vaccines are highly efficacious and safe. Primary series of two or three doses protect approximately 95% of infants [4–8]. Universal infant Hib immunization has proven to dramatically reduce Hib invasive disease [9–13] through direct vaccine protection and an important herd effect related to the reduction in Hib nasopharyngeal carriage in the community [12,14–16]. Adverse events are rare, and Hib vaccine is contraindicated only for persons with hypersensitivity to any of the vaccine's components [8,17]. The World Health Organization (WHO) recommends the introduction of Hib vaccines worldwide [1]. Furthermore, the Global Alliance for Vaccines and Immunization (GAVI Alliance)—an organization that aligns public and private resources in a global effort to create greater access to the benefits of immunization—considers Hib vaccine introduction in the world's poorest countries to be a top priority [18]. Prior to vaccine introduction, an estimated 20,000 cases of Hib meningitis were estimated to occur in countries of Latin America and the Caribbean (LAC) annually, based on an overall Hib meningitis incidence of 35 per 100,000 children aged 0–4 years [19]. Another 20,000 cases of invasive Hib disease were estimated to occur in the United States annually [20]. Most cases occurred in children aged less than 24 months, with at least 60% of cases occurring in children aged 0–11 months in half of the studies. The annual mortality rate for Hib meningitis in children aged less than five years was estimated to be around two per 100,000 in the Western Hemisphere [21]. Summary Points Hib vaccine introduction in countries of Latin America and the Caribbean has substantially reduced morbidity and mortality due to invasive Hib infections. All Latin American and Caribbean countries but one include Hib vaccine in their routine immunization schedule for infants. Factors that favored this region-wide Hib vaccine adoption include strong political will, data supporting Hib disease burden and impact in early adopting countries, and experience exchange among countries. Financial sustainability when introducing the more expensive Hib vaccine was critical for ensuring successful vaccine introduction in all countries. Efforts are still needed to improve vaccination coverage and to strengthen invasive bacterial disease surveillance in developing countries. In this article, we review the progress of vaccine introduction, lessons learned, and remaining challenges regarding Hib vaccination in the Americas, with emphasis on LAC countries. We expect that this updated and summarized information on Hib vaccination will serve as a useful reference to public health officials and policy makers from other regions who face the challenge of introducing Hib and other new or underutilized vaccines.