Hepatitis B virus (HBV) causes life-threatening liver disease. It is transmitted through a horizontal route or a mother-to-infant route, and the latter is the major route in endemic areas. Prevention of HBV infection by immunization is the best way to eliminate HBV-related diseases. The HBV vaccine is the first human vaccine using a viral antigen from infected persons, which is safe and effective. Either passive immunization by hepatitis B immunoglobulin (HBIG) or active immunization by HBV vaccine is effective, and a combination of both yields the best efficacy in preventing HBV infection. The impact of universal HBV immunization is huge, with 90%-95% effectiveness in preventing chronic HBV infection. It is the first cancer preventive vaccine with a protective efficacy against hepatocellular carcinoma (HCC) of ∼ 70%. Nevertheless, further effort is still needed to avoid vaccine failure and to increase the global coverage rate.