The availability of hundreds of different adjuvants has prompted a need for identifying rational standards for selection of adjuvant formulations based on safety and sound immunological principles for human vaccines. Although many of the mechanisms of adjuvants have been elucidated, meaningful comparisons between different adjuvants derived from in vitro studies, or from studies using adjuvants in rodents or other animals, are often not predictive for safety, adjuvant effects, or vaccine efficacy in humans. A highly efficient and cost-effective method for comparison of adjuvants with a new antigen is to conduct multiple small-scale, phase 1, comparative studies in humans with a new antigen, using adjuvants previously found to be safe with other antigens in human trials. Studies in which highly immunogenic and safe adjuvant formulations have been evaluated in comparative adjuvant trials in humans using a single candidate vaccine antigen against malaria, HIV, and prostate cancer with multiple adjuvants are reviewed.