This guidance document aims to help researchers to consider, examine, and address ethical issues associated with human enhancement. Human enhancement refers to a wide field of interventions and technologies that aim at improving human beings beyond what might otherwise be considered typical or average. The guidance in this document is designed to be cross-disciplinary, and not limited to a particular field of science, engineering or medicine. It aims to cover all fields in research and development (R&D) where human enhancement potential may occur. Although it has wider application, this document has been composed for Horizon Europe ethics review and it thereby also complements other documentation for the ethics review procedure in Horizon Europe. This document is intended for the following types of projects: (1) Projects in which human enhancement is an explicit aim, either through research intended to facilitate human enhancement applications, or through the development of products or techniques intended for human enhancement; (2) Projects that have unforeseen, unpredicted or unintended potential enhancement applications, by which is meant that research and/or development is undertaken for therapeutic or other non-enhancement purposes, but the results of the project also have a clear potential for human enhancement.