Optimization of the immunogenicity of many new-generation vaccine formulations, including combination vaccines, will require the use of immunologic adjuvants other than the aluminum compounds in today's licensed vaccines. The selection of adjuvants for use in vaccine formulation may be as critical as the choice of the vaccine antigens themselves in providing optimal efficacy for the target populations, vaccine compliance, and cost. Adjuvants have diverse mechanisms of action and must be selected for use based on the immune responses desired for a particular candidate vaccine. Recent advances in the number and variety of adjuvants available for clinical evaluation coupled with the increased understanding of their mechanisms of action encourage the inclusion of adjuvants as part of rational vaccine design. Finally, the proposed standardized methods to evaluate adjuvant safety should be implemented for human candidate vaccines formulated with novel adjuvants.