The year 2012 marks the eightieth anniversary of the beginning of the U.S. Public Health Service’s (PHS) study on the effects of untreated syphilis in Tuskegee, AL, which lasted from 1932 to 1972. The research continued after penicillin became widely available and was known to be an effective treatment for syphilis. To justify the experiments, the PHS argued that the study was a never-to-be-repeated opportunity. Did the U.S. government continue to take advantage of never-to-be-repeated opportunities in medical research by using unethical justifications? This manuscript will explore how America’s growing understanding of human research and the rights of human subjects have mirrored the growth of regulatory law and jurisprudence since the Tuskegee Study. We will examine PHS human research experiments in Guatemala from 1946 to 1948, as well as the U.S. Department of Justice’s decision not to prosecute members of the Japanese Army despite having received information on human experiments they conducted on World War II Prisoners of War (POWs). We recognize that numerous events have contributed to current human research practices and it would be impossible to discuss every significant topic. We submit that society’s ethical considerations regarding human research have progressed over the past eighty years. In this article we concentrate on the growing protections of the right to informed consent. We contend that constant and consistent oversight by the three branches of U.S. government is necessary to ensure human rights protection of those classes least able to protect themselves and prevent another Tuskegee Study.