Routine pediatric vaccinations have resulted in dramatic declines in the incidence and complications of several vaccine-preventable diseases (VPDs) over the past fifty years. At the same time, the prolongation of life expectancy and the large number of adults living with chronic medical conditions changed the demographic profile and, accordingly, the healthcare needs. The recognition of the burden and effects of several VPDs in adults and in particular risk groups and the comprehension of the age-dependent deterioration of immune responses have driven the extension of routine vaccination programs beyond adolescence. In addition, several VPDs emerged or re-emerged over the past decades, and new vaccines have been developed or are under clinical assessment. Currently, vaccination programs in many countries include vaccinations for adults, aiming to expand and strengthen protection throughout the lifespan and promote healthy aging. Moreover, there are needs for new or more effective vaccines against common or emerging pathogens and public health threats, including chronic diseases. This article reviews the current status of several adult vaccinations and discusses challenges for adult vaccinations, including new vaccines, emerging or re-emerging VPDs, and strategies to overcome low vaccination rates.