An effective vaccine usually requires more than one time immunization in the form of prime-boost. Traditionally the same vaccines are given multiple times as homologous boosts. New findings suggested that prime-boost can be done with different types of vaccines containing the same antigens. In many cases such heterologous prime-boost can be more immunogenic than homologous prime-boost. Heterologous prime-boost represents a new way of immunization and will stimulate better understanding on the immunological basis of vaccines.