While Burkholderia pseudomallei, the causative agent of melioidosis, is becoming increasingly recognized as a significant cause of morbidity and mortality in regions to which it is endemic, no licensed vaccine preparation currently exists for immunization against the disease. Therefore, one of the primary goals of our research has been to identify and characterize antigens expressed by B. pseudomallei isolates for the intended purpose of developing a vaccine construct that can be used to actively immunize specific high risk populations against the disease. By utilizing a combination of biochemical, immunological and molecular approaches, our studies now indicate that some of the most promising candidates for this task include flagellin proteins and the endotoxin derived O-polysaccharide (PS) antigens expressed by the organism. In this review, we have attempted to summarize the current status of B. pseudomallei research while endeavoring to provide a rationale for our approach towards the development of a melioidosis vaccine.