The GRACIOUS project has developed a highly innovative science-based framework that supports the assessment of risk posed by the ever increasing array of nanomaterials on the market and under development. The Framework streamlines the process for assessing their risk by logically grouping nanomaterials thereby allowing extrapolation between (read-across) nanomaterials and reducing the need to assess exposure to and toxicity on a case by case basis. The Guidance Document introduces a new user of the Framework to the essential steps they will need to take to use the Framework to support their grouping and read-across decisions and uses worked examples to show how these steps have been done practically in the GRACIOUS project.