This document is intended to provide universal Guiding Principles that should be considered when developing or augmenting systematic approaches to Weight of Evidence (WoE) for chemical evaluation and Key Elements to formulating a systematic approach to WoE. The ultimate goal is to facilitate that regulators follow a consistent, clear and transparent delivery of evidence using the Principles and Elements described in this document. This can be especially helpful for countries with no existing WoE frameworks or those looking to augment their approaches. It also allows for stakeholders to understand a WoE decision-making process, including potential for unreasonable bias. These Guiding Principles and Key Elements can be employed to develop frameworks that range from simple and pragmatic approaches to more elaborate systems, depending on the context.