Japanese encephalitis (JE) is a significant human health concern in Asia, Indonesia and parts of Australia with more than 3 billion people potentially at risk of infection with Japanese encephalitis virus (JEV), the causative agent of JE. Given the risk to human health and the theoretical potential for JEV use as a bioweapon, the development of safe and effective vaccines to prevent JEV infection is vital for preserving human health. The development of vaccines for JE began in the 1940s with formalin-inactivated mouse brain-derived vaccines. These vaccines have been shown to induce a protective immune response and to be very effective. Mouse brain-derived vaccines were still in use until May 2011 when the last lots of the BIKEN(®) JE-VAX(®) expired. Development of modern JE vaccines utilizes cell culture-derived viruses and improvements in manufacturing processes as well as removal of potential allergens or toxins have significantly improved vaccine safety. China has developed a live-attenuated vaccine that has proven to induce protective immunity following a single inoculation. In addition, a chimeric vaccine virus incorporating the prM and E structural proteins derived from the live-attenuated JE vaccine into the live-attenuated yellow fever 17D vaccine virus backbone is currently in clinical trials. In this article, we provide a summary of JE vaccine development and on-going clinical trials. We also discuss the potential risk of JEV as a bioweapon with a focus on virus sustainability if used as a weapon.