This guide will serve as a resource for agencies that are required to, or elect to, set performance measures and targets for the safety performance of a road network or jurisdiction. The guide discusses the importance of setting safety targets and how safety target setting aligns with the Highway Safety Improvement Program (HSIP) and Highway Safety Plans (HSP). The guide presents a framework to facilitate target setting and the integration of safety targets into planning and programming activities. Finally, the guide addresses the data needs for evidence-based target setting and several technical, data-driven methods for target setting. The intended audience is State transportation agencies, metropolitan and regional planning organizations, and local government agencies.