Pathogens, such as bacteria, viruses, protozoa and fungi, generate molecules that provide them with a selective advantage, often at the expense of the host. These molecules, or virulence factors, enable pathogens to colonize the host through several mechanisms. Some molecules offer the pathogen an advantage through better adhesion to host tissues, or superior invasive capability. Some allow the pathogen to evade or suppress the host's immune system. Some molecules enable intracellular parasites to disable cytoprotective mechansims, by re-directing the host phagocytic vesicles. Many of these molecules are proteins that are exported to the cell's surface or are secreted. As unlikely as it seems, GAPDH appears to play a role as a virulence factor in a number of pathogenic organisms by the mechanisms just described. This highly conserved protein is found on the outer surface or as a secretory product of these organisms. The process by which pathogenic GAPDH, which has >40 % sequence identity to human GAPDH, is exported and attached to the outer surface of cells remains unknown. This chapter also presents a previously unpublished proposed docking sequence on GAPDH. There is also discussion of the potential of using the antigenic properties of pathogenic GAPDH for medical as well as for veterinary purposes.