Schistosomiasis continues to be a significant public health problem in tropical countries such as Brazil. Even though drug treatment in endemic areas has been shown to be efficient for controlling morbidity, it does not reduce prevalence due to constant reinfections. Therefore, a long-term disease control strategy is needed combining mass chemotherapy with a protective vaccine. Although the field of vaccine development has experienced more failures than successes, encouraging results have been obtained in recent years using defined recombinant derived Schistosoma mansoni antigens. This article primarily reviews the progress in the development of a vaccine against S. mansoni in Brazil. We discuss here different forms of vaccine tested in Brazil in pre-clinical trials and immunologic studies performed with patients in endemic areas of schistosomiasis. Lastly, we reviewed the S. mansoni genomic projects developed in the country and the recent advances in the identification of new molecules with potential as vaccine targets.