Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. The disease affects many areas of the world, often causing extensive epizootics in livestock, mostly farmed cattle and swine, although sheep, goats and many wild species are also susceptible. In countries where food and farm animals are essential for subsistence agriculture, outbreaks of FMD seriously impact food security and development. In highly industrialized developed nations, FMD endemics cause economic and social devastation mainly due to observance of health measures adopted from the World Organization for Animal Health (OIE). High morbidity, complex host-range and broad genetic diversity make FMD prevention and control exceptionally challenging. In this article we review multiple vaccine approaches developed over the years ultimately aimed to successfully control and eradicate this feared disease.