Poor test specificity when resolving positive serology, due to infection with cross-reactive bacteria and vaccination with smooth Brucella strains, is also an impediment to efficient disease eradication. A case for the development of novel discrete epitope antigens to address this is presented alongside in silico methods of selection and tools that enable increased analytical sensitivity that may be required to detect relatively low, but potentially significant, analytes. References have been drawn from the study of brucellosis wherever possible. However, in some cases new technological developments worthy of discussion have been included via the use of pertinent alternative examples. In conclusion, despite developments and innovations the classical serological tests seem under no imminent danger of mass extinction but there is potential for significant improvement and supplementation.