To assist PMs, system design engineers, and system safety engineers in addressing the unique aspects of the holistic Unmanned Systems (UMSs) technology development environment, the Office of the Secretary of Defense (OSD) issued a call to government, industry, and academia to develop safety guidance. The objective of this guidance is to ensure the design and development of UMSs that incorporate the necessary safety design rigor to prevent potential mishaps, or mitigate potential mishap risk. OSD directed this safety guidance also consider real and potential Concepts of Operation (CONOPS) of UMSs and establish fundamental operational safety requirements necessary to support safe operation of the UMS. This guidance provides a generic set of safety precepts and safety design considerations and establishes a starting point toward ensuring safety is a fundamental pillar of the acquisition process and incorporates those necessary design considerations to safely sustain UMSs.