Although vaccine adjuvants have been used for almost a century, alum is the only adjuvant licensed by the US FDA for human vaccine use. Many adjuvants studied to date have generalized inflammatory properties and lack specificity in terms of targeting immune compartments and cell populations. Indeed, such adjuvants have often been crude in formulation, their effects usually restricted to T-helper 2-type immunity and their use limited owing to inherent toxicity. However, recent advances in immunology have resulted in a number of potential adjuvant candidates that are able to modulate the immune response in a more controlled and specific manner. These novel adjuvants are attractive for inclusion in current and future vaccine strategies since they have better-defined mechanisms of action. In this article, we review several compounds that target specific immune components, such as cells, receptors or signaling pathways, and have termed such reagents 'smart adjuvants'.