While the incidence of fraud in science is well documented, issues related to the establishment of innocence in cases of fallacious allegations remain unaddressed. In this article, the author uses his own experience to examine issues that arise when investigators are falsely accused of scientific fraud. Investigators must understand the processes in place to protect themselves against false accusations. The present system takes a position of guilty until proven innocent, a concept that is antithetical to American principles of jurisprudence. Yet this stance is acceptable as a requirement for membership in the scientific community, more reflective of the rules within a guild organization. The necessity for proof of innocence by members of the scientific community carries obligations that transcend normal legal assumptions. Scientists must safeguard their reputations by organizing and maintaining all original image files and data relevant to publications and grant proposals. Investigators must be able to provide clear documentation rapidly whenever concerns are raised during the review process. Moreover, peer-reviewed journals must be diligent not only in the identification of fraud but also in providing rapid due process for adjudication of allegations. The success of the scientific guild rules of conduct lies in the practice of due diligence by both scientists and journal editors in questions of scientific misconduct.