This publication provides comprehensive guidance on establishing and implementing a trustworthiness programme for nuclear security with a focus on preventive and protective measures to address threats posed by insiders. It outlines practical approaches for assessing and determining the trustworthiness of individuals, as well as for monitoring their ongoing reliability and integrity. It also offers guidance on granting access authorization to nuclear material, other radioactive material, associated facilities and activities, as well as sensitive information and digital assets, including those that can be accessed remotely. Furthermore, it demonstrates how the trustworthiness programme forms an integral part of a defence in depth strategy within the broader framework of nuclear security.