Foot-and-mouth disease (FMD) is the most highly contagious disease affecting livestock resulting in a significant adverse economic impact worldwide. Disease outbreaks in previously FMD-free countries are initially controlled by the culling of infected and in-contact animals, restriction of susceptible animal movement, and vaccination with an inactivated whole-virus antigen preparation. With increasing trade, commerce globalization, and people migration, it is likely that more inter-pool viral exchanges and spillovers will occur posing a greater threat to both, endemic and non-endemic regions, mostly due to the limited antigenic coverage of current vaccines. Currently available inactivated FMD vaccines have a number of disadvantages, including incomplete inactivation of the virus, they require multiple vaccination to maintain good levels of immunity and periodic inclusion of new viral strains into the vaccine formulation to cover new FMDV subtypes against which existing vaccines no longer protect and lack differentiation of infected from vaccinated animals (DIVA). The essential aim of DIVA strategy is realization of the so-called “vaccinate-to-live” policy, which is based on the principles that vaccinated animals exposed to FMDV will not transmit the virus. To address the shortcomings of inactivated vaccines, many efforts are currently devoted to developing novel FMD vaccines, including attenuated and marker inactivated vaccines, recombinant protein vaccines, synthetic peptide vaccines and empty capsid vaccines. Novel vaccine platforms offer promising alternatives for effective FMD control. It is likely that in the near future, multiple FMD vaccine approaches will compete for diverse markets, providing fit-for purpose solutions to evolving challenges in preventing and controlling FMD worldwide.