History of vaccine development was presented. Introduction of gene technology since early 1980's was described together with its advantages and problems, and success of Hbs vaccine by gene technology was described. For further success, development of more efficient and safe immunoadjuvant has been awaited. As new approaches, development of DNA vaccines and mucosal vaccines have been studied. Difference of mechanism of immune response by live viral vaccine and killed or subunit vaccine was described. Live virus infect immunocompetent cells and viral antigen produced in them (endogeneous protein) prime cytotoxic lymphocyte (CTL, CD8) together with MHC class I antigen, while foreign protein is presented to CD4 lymphocyte together with MHC class II antigen after digestion by lysozyme. DNA vaccine seems to mimic live viral vaccine in priming CTL. However, long-term safety must be considered carefully for general use, particularly for children. Benefit/Risk and Cost/Effectiveness ratios should be taken into consideration for development of vaccines, and pathogenesis of diseases should also be well understood for evaluation of the vaccine. Live varicella vaccine has widely been used for prevention of chickenpox, and it is expected that vaccination of children would reduce the incidence of zoster in their later life. Immunization trial of the elderly with varicella vaccine to prevent zoster, particularly post herpetic neuralgia, is being done in a large scale in USA.