Infections with arthropod-bome viruses are increasing globally as a result of climate and demographic changes, global dispersion of insect vectors, and increased air travel. The similar symptomatology of arboviral diseases and the cocirculation of different arboviruses in Africa, Asia, and South America complicate diagnosis. Despite the high sensitivity and specificity of molecular diagnostic tests, their utility is limited to the short viremic phase of arbovirus infections, and therefore the diagnosis of infection is frequently missed in clinical practice. Conversely, the duration of antibody responses provides a wider window of opportunity, making diagnosis more dependent on IgM/IgG detection. This review discusses the issues underlying the low specificity of antibody-detection assays, and addresses the challenges and strategies for discovering more specific biomarkers to enable a more accurate diagnosis.