While vaccination continues to be the most successful interventionist health policy to date, infectious disease remains a significant cause of death worldwide. A primary reason that vaccination is not able to generate effective immunity is a lack of appropriate adjuvants capable of initiating the desired immune response. Adjuvant combinations can potentially overcome this problem; however, the possible permutations to consider, which include the route and kinetics of vaccination, as well as combinations of adjuvants, are practically limitless. This review aims to summarize the current understanding of adjuvants and related immunological processes and how this knowledge can and has been applied to the strategic selection of adjuvant combinations as components of vaccines against human infectious disease.