Infectious agents are major contributors to disease in individuals at the extremes of the aging spectrum. This is in part due to the suboptimal responsiveness of the immune system in these populations. While vaccines represent the optimal approach for preventing disease, unfortunately the impairment in immunity extends to vaccine responsiveness and as a result these populations do not benefit from vaccine mediated protection to the same level as individuals outside of these age extremes. To overcome these barriers, it is clear that new approaches, e.g. adjuvants, delivery mechanisms, altered antigen doses and carriers, are sorely needed.