The considerable advances made in the fields of molecular biology, genomics, proteomics and protein engineering have led to the identification of a vast range of potential vaccine antigens for a host of man's most serious diseases. However, experience informs us that vaccines based on recombinant proteins and synthetic peptides lack the immunogenicity of the whole, killed pathogens used in traditional vaccines and, as such, clinical use of these immunogens remains negligible. In order to fully realize the potential benefits of recombinant antigen-based vaccines there is a pressing need to identify powerful adjuvants which can safely enhance these weak responses with a minimum of undesirable side effects. Adjuvant research represents a vibrant and fast moving field and recent developments suggest the goal of generating effective, safe and affordable ways of enhancing immune responses appears to be almost within our grasp. The purpose of this article is to review recent advances in adjuvant development using approaches that directly exploit the immune system's own co-stimulatory pathways to exert their function; with a particular emphasis on CD40 and CD28 based therapies.