New generation vaccines, particularly those based on recombinant proteins and DNA, are likely to be less reactogenic than traditional vaccines but are also less immunogenic. Therefore, there is an urgent need for the development of new and improved vaccine adjuvants. Adjuvants can be broadly separated into two classes based on their principal mechanisms of action: vaccine delivery systems and immunostimulatory adjuvants. Vaccine-delivery systems generally are particulate (e.g., emulsions, microparticles, iscoms, and liposomes) and function mainly to target associated antigens into antigen-resenting cells. In contrast, immunostimulatory adjuvants are derived predominantly from pathogens and often represent pathogen-ssociated molecular patterns (e.g., lipopolysaccaride, monophosphoryl lipid A, CpG DNA). which activate cells of the innate immune system. Recent progress in innate immunity is beginning to yield insight into the initiation of immune responses and the ways in which immunostimulatory adjuvants may enhance this process. The discovery of more potent adjuvants may allow the development of prophylactic and therapeutic vaccines against cancers and chronic infectious diseases. In addition, new adjuvants may also allow vaccines to be delivered mucosally.