Hepatitis B virus (HBV) is the most common cause of chronic viral hepatitis and hepatocellular carcinoma in the world. Worldwide, more than 250 million people are chronically infected with HBV, causing nearly 780,000 deaths each year, and mother-to-child transmission (MTCT) accounts for more than one-third of chronic HBV infections. Universal vaccination in neonates is the most effective strategy for eliminating infections worldwide. Maternal antiviral treatment during the antepartum/postpartum period for mothers with high HBV viral loads is effective in preventing HBV MTCT. Full immunization coverage is currently the only way to reach the goal of eradicating HBV infection. Operational research and, in some resource-limited settings, international funding may be essential to bring the vaccine where neonates and infants need it, including remote locations where home births are common. Continued improvements in the coverage and timeliness of HBV vaccination and education of clinicians about its importance are needed.