There are no commercially available vaccines for the prevention of coccidioidomycosis. This fungal infection, endemic to the Southwestern US and parts of Latin America, is estimated to cause ≥150 000 new infections each year, with exposure possible to approximately 20 million individuals in the US alone. The lack of highly effective antifungal therapies also makes the development of a vaccine against this disease desirable. Vaccine research over the last 60 years has progressed from the use of whole-killed cells, to subcellular fractions, to recombinant proteins, and is now utilizing molecular techniques to prepare multivalent recombinant protein vaccines, DNA-based vaccines, and dendritic cell vaccines. In addition, newer studies are examining glycan–protein conjugate vaccines. Each has been shown to be effective in animal models of infection, but none have progressed to the clinical trial stage. Continued improvements are needed in the choice of antigens used, composition, adjuvant, and route of administration. In this article, we will review the current status of vaccine research against coccidioidomycosis. J Invasive Fungal Infect 2011;5(4):99–109.