Scrub typhus, an acute, febrile and potentially fatal disease, caused by infection with the obligate intracellular bacterium Orientia tsutsugamushi, is commonly seen in the Asia-Pacific region. This disease can be handled successfully with rapid diagnosis, proper antibiotic treatment, and rodent and chigger control. However, recent reports of scrub typhus outbreaks in endemic areas, and a decreased effectiveness of antibiotic treatment suggest a continued need for a suitable vaccine. This review describes the early and recent attempts in making prophylactic preparations to prevent scrub typhus, the successes and failures of these attempts, and future directions of scrub typhus vaccine development.