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Zika virus disease provides the latest example of a critical nexus between public health and clinical practice. Interpreting Zika virus test results is complicated by the absence of a single testing approach with superior validity across contexts and populations. Molecular tests are highly specific, variably sensitive, and have a short window period. Serologic tests identify antibodies against Zika virus and are more likely than molecular tests to cross-react with other related viruses, reducing specificity. The type of test performed and timing relative to possible Zika virus exposure depend on public health guidance, testing algorithms, test availability, and capacity. Guidance from the Centers for Disease Control and Prevention and local health departments have changed throughout the course of the US epidemic based on prevalence, geography, and clinical concerns. Women with a low pretest probability of infection should be counseled against testing. Women with a high pretest probability of Zika virus infection should still receive enhanced prenatal monitoring and newborn evaluation, regardless of the test result. An appropriate interpretation of results depends on what tests are used, patient characteristics, and reasons for testing. Clinicians should take these factors into account in shared decision making discussions with pregnant women about Zika virus testing.