The increasing threat to the human population posed by new or resurgent infectious diseases, coupled with an alarming rise in the incidence of antibiotic-resistant microbes, has created a tremendous need for new vaccines. A critical element in the development of these new vaccines is the ability, via adjuvants, to potentiate and focus the immune response to the vaccine in beneficial ways so that optimal protection can be achieved. One promising candidate adjuvant in this regard is MPL® immunostimulant, a monophosphoryl lipid A preparation derived from the lipopolysaccharide (LPS) of Salmonella minnesota R595. MPL® is being considered as an adjuvant for a number of human vaccines, and experience to date has shown that it is safe, well tolerated, and able to provide a heightened immune response to coadministered antigens. In this chapter, various topics related to the preparation, formulation, and use of MPL® as an adjuvant will be discussed. In addition, our current knowledge of the mechanisms of action of MPL® will be reviewed.