The forty year Tuskegee Syphilis Study has become the American metaphor for medical racism, government malfeasance, and physician arrogance. The subject of histories, films, rumors, and political slogans, it received an official federal apology from President Bill Clinton in a White House ceremony. The author offers an analysis of the notorious study of untreated syphilis, which took place in and around Tuskegee, Alabama, from the 1930s through the 1970s. The study involved hundreds of African American men, most of whom were told by doctors from the U.S. Public Health Service that they were being treated, not just watched, for their late stage syphilis. She examines the study and its aftermath from multiple perspectives to explain what happened and why the study has such power in our collective memory. She follows the study’s repercussions in facts and fictions. She highlights the many uncertainties that dogged the study during its four decades and explores the newly available medical records. She uncovers the different ways it was understood by the men, their families, and health care professionals, ultimately revising conventional wisdom on the study. This work illuminates the events and aftermath of the study and sheds light on the complex knot of trust, betrayal, and belief that keeps this study alive in our cultural and political lives.