Hepatitis B virus is a substantial contributor to cirrhosis and hepatocellular carcinoma (HCC) globally. Vaccination is the most effective method for prevention of hepatitis B and its associated morbidity and mortality, and the only method to prevent infection with hepatitis D virus. The hepatitis B vaccine has been used worldwide for more than four decades; it is available in a single- or triple-antigen form and in combination with vaccines against other infections. Introduction of the vaccine and administration at birth led to sustained decline in mother-to-child transmission, chronic hepatitis B, and HCC, however, global birth dose coverage remains suboptimal. In this review we will discuss different hepatitis B vaccine formulations and schedules, vaccination guidelines, durability of the response, and vaccine escape mutants, as well as the clinical and economic benefits of vaccination.