This year the world commemorates the beginning of the tragic USPHS syphilis experiments that occurred in Tuskegee, Alabama from 1932 to 1972. In light of this sobering anniversary, this article will briefly examine four studies: the already mentioned USPHS syphilis studies in Tuskegee, the Nazi Holocaust Experiments and the resulting Doctors' Trial at Nuremberg, the USPHS study on sexually transmitted diseases in Guatemala, and the Pfizer Trovan study in Nigeria. By reflecting critically upon these four tragic events in the history of research, the research community is reminded of its non-negotiable, ethical responsibility to protect human subjects, particularly those who are most vulnerable.