The subunit recombinant hepatitis B virus (HBV) vaccines available in the US differ in hepatitis B surface antigen content. Clinical studies have linked higher antigen formulations with enhanced peak protective antibody levels. This is important for the elderly, smokers, the obese, and the immunocompromised. Immune memory, which is responsible for prolonged protection when HBV vaccine-induced antibody levels become undetectable, may be related to antigen persistence on immunologically active cells. Antigen persistence may be related to antigen content of the vaccine and thereby influences the duration of immunity. Proof of this concept will require additional studies of immune memory in HBV.