Scientists are usually considered to be respected sources of information and there is the understanding within the scientific community that data must not be inappropriately manipulated or falsified. When this essay was first composed in 2001, there were very few written guidelines for scientists. Now some of the major professional societies have issued policy statements regarding digital imaging, and many scientific journals have revamped their instructions to authors to provide clearer guidance of how they require images to be handled. Publications like the Journal of Cell Biology have begun testing images in accepted articles to ensure compliance with their guidelines and the Office of Research Integrity (HHS) has been watching this issue closely. In this author’s experience the inappropriate manipulation of scientific digital images typically does not arise from an intent to deceive or to obscure information. More often the inappropriate manipulations are simply due to ignorance of basic principles. It seemed to this author that often what is needed is an explanation of why manipulations are right or wrong. These twelve guidelines are an attempt to address this issue. It should be noted that the author has extensive experience in the microscopic imaging of biological specimens and these guidelines reflect his personal experience in this field.