Systematic fraud threatens the integrity of science, with papers and reviews distorting the evidence base in medicine and global health. Open science and data transparency are the most powerful tools in the fight against fraudulent publication activities. Data transparency must be considered the first line of defense against wrongdoing. Only through open data and coordinated measures can trust in research and its impact on health be ensured. The article was authored by PLOS Medicine Executive Editor Helen Lumbard and co-authored by Section Editor-in-Chief Daniel Routledge. The scientific community is urged to stand up against research fraud and paper mills by establishing robust systems of data sharing and transparency.