Growing regulatory burdens, payment model changes, and increased complexity in laboratory medicine have contributed to an increased reliance on reference laboratories. Although reference laboratories often offer rapid, low cost, high quality testing, outsourcing laboratory tests can create quality and patient safety vulnerabilities particularly in the pre-analytic and post-analytic phases of the test cycle. Disconnects in governance, policy, and information technology between the reference laboratory and the referring provider conspire to increase risk. Laboratory leaders seeking to reduce risk and improve quality must ensure clear and collaborative oversight, monitor meaningful quality metrics, and integrate feedback from ordering providers.