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As infectious disease diagnostics increasingly incorporates molecular techniques, there are unique preanalytical concerns that must be considered. First, noninvasive specimen types that may be inadequate for culture-based diagnostics may be acceptable when using molecular tests. Second, specimen containers must be evaluated for the presence of substances that may interfere with amplification or sequencing reactions. Finally, the capacity of transport, storage, and processing conditions to maintain nucleic acid integrity and avoid contamination must be assessed. This review explores these issues and the effects they may have on result quality., Competing Interests: Disclosure A. Misra has no disclosures. E.A. Powell has received research funding from GenMark Diagnostics., (Copyright © 2023 Elsevier Inc. All rights reserved.)