This handbook, developed by the European Network of Research Integrity Offices (ENRIO), presents information on best practices regarding the protection of whistleblowers in research. The handbook aims to guide research performing institutions on how to implement a whistleblowing management system. Its contents may also be useful for research funding organisations as they monitor research projects or individual researchers and receive communications related to potential wrongdoing in funded research. The handbook is also directed at researchers, the interested public and potential whistleblowers. It offers some considerations for those contemplating reporting alleged research misconduct, along with potential issues that might arise during and after an investigation.