The vaccines has been developed over the first two hundred years since Jenner's smallpox vaccination. In modern days, vaccination has had the largest impact on the incidence and persistence of infections. Although natural infection induces lifelong immunity, the assumption that the vaccine also confers permanent protection has been reconsidered following outbreaks of measles in students who had been vaccinated 15-20 years prior to infection in the US in the 1980s. Clinical studies have proposed several mechanisms such as vaccine failure in some individuals and the subsequent loss of immunity after vaccination. An ideal vaccine is relatively easy to define, but few real vaccines approach the ideal. Many difficulties account for the failure in producing these ideal vaccines. However, recent advances in methods for studying immune response to pathogens have provided a better understanding of immune mechanisms. Based on these findings, the development of good vaccine formulations allowing stimulation of optimal and prolonged protective immunity and immunization policies or schedules should lead to the introduction of vaccines for previously resistant organisms.