A precedent setting legislative mandate under the Canadian Environmental Protection Act 1999 to establish priorities for assessment based on systematic consideration of all of the approximately 23,000 Existing Chemicals in Canada required the development and refinement of methodology in a number of important areas. This included development of simple and complex exposure and hazard tools for priority setting which draw maximally and efficiently on available data to systematically identify substances that are highest priorities in relation to their potential to cause adverse effects on the general population. The hierarchical approach in the simple and complex hazard tools described here efficiently and effectively sets substances aside as non-priorities, or prioritizes them for consideration additionally in assessment. The hazard tools efficiently incorporate previous work, contributing to consistency internationally, and involve hierarchical consideration of sources of information based on their relative weighting. They are health protective, based on their incorporated degree of conservatism, and provide direction for additional assessment for substances deemed to be priorities. Although designed for prioritization of Existing Substances in Canada, these tools have potential for broader application in other national and international programs to provide focus and increase efficiency in human health risk assessment.