During the past decade, tremendous progress has been made in process development allowing for the production of large quantities of recombinant antigens, as well as in the understanding of the immune mechanisms underlying protection. Parallel to this, various and numerous adjuvant systems have been developed and tested in animal models and in clinical trials but have rarely induced protection. This review will discuss the development of a new adjuvant system (AS02) in combination with a malaria vaccine antigen candidate. To date, this vaccine is the only one to demonstrate protection in man in artificial challenge as well as in natural field trials. It has been established that this adjuvant system is capable of eliciting high antibody titers along with strong cell-mediated immunity which both contribute to the efficacy of the vaccine.