Zika virus is a flavivirus that is spread by the bite of infected Aedes mosquitoes. The current outbreak and swift dissemination/spread of Zika virus (ZIKV) and its linkage to birth defects and neurological syndromes has prompted the development of novel diagnostic tests. Because ZIKV is serologically similar to other flaviviruses such as dengue virus (DNV), cross-reactivity occurs in diagnostic tests and can result in misdiagnoses. This is especially evident in populations that live in dengue-endemic regions or have received heterologous flaviviral vaccines (i.e., yellow fever 17D). CDC researchers have developed seven monoclonal antibodies (mAbs) that are highly specific to the Zika virus non-structural protein 1 (NS1 protein) without cross-reactivity to other flaviviruses. These antibodies can be used to create rapid and more specific diagnostic tests. Data to support ZIKV-specific and DENV-specific mAbs include immunofluorescence, immunoblots of r-protein and viral lysates, recombinant proteins in label-free binding, and indirect ELISA studies. Platforms such as lateral flow diagnostics and nanotechnology devices capable of interfacing with smartphone/digital devices are possible.