Zika virus (ZIKV) captured mass public attention in 2014–16 due to its potentially devastating teratogenic effects in unborn babies. Although recent years show a decline in disease activity as ZIKV settles into endemic New World cycles, the significant challenges that originally complicated its diagnosis remain, and linkages to foetal microcephaly make safe, accurate, and timely detection especially important. The present chapter seeks to define current direct and indirect immunological detection methods for ZIKV in the context of cross-reactive viral relatives, and will consider the utility and difficulties associated with each practice in resource-rich and resource-poor settings. A synthesis of general diagnostic approaches will more specifically cover immunological techniques spanning from serology to antigen-based immunoassay against the backdrop of common luminescent, fluorescent, and colorimetric output signal types. This analysis uses the diagnostic landscape of Zika virus as a ready template for the classification and contextual understanding of many methods within viral diagnostics.