The age-associated increased susceptibility to infectious disease would suggest that vaccination should be a route to promote healthy aging and keep our seniors autonomous and independent. While vaccination represents a cost-effective and efficient strategy at community level, the ability of the immune system to mount a protective immune response is still unpredictable at the level of the individual. Thus, at a similar age, some individuals, including the elderly, might still be 'good' responders while some other, even younger, would definitely fail to mount a protective response. In this review, the current burden of vaccine-preventable diseases in the aging and aged population will be detailed with the aim to identify the ideal vaccine candidates over the age of 50 years. This article will conclude with potential strategies to reduce, as best as possible, this burden and the imperative need to overcome barriers in extending current vaccine coverage towards to a lifelong vaccine schedule.