This document provides guidance for laboratory leadership and personnel to develop, implement, and sustain effective emergency operations plans (EOPs) that pertain to all hazards (eg, emerging public health threats, natural and manmade disasters, unexpected system failures) and support operations through the entire laboratory path of workflow (preexamination, examination, and postexamination). The discussion of the examination phase focuses on general principles and not on specific diagnostic tests. General aspects of this document could pertain to hospital laboratories, independent referral laboratories, and public health laboratories (PHLs). Additional emphasis is given on how to interact with governmental Laboratory Response Networks (LRNs). This document should be used as a guideline to develop a local or site-specific EOP. Laboratory analytical aspects involving biothreat incidents are not addressed. Although certain aspects of the guideline focus on emergency operational challenges confronting hospital-based laboratories, guidance for clinical laboratory preparedness for referral (independent) laboratories is also provided.