The story of U=U began in the 1990s when it became apparent that the risk of sexual transmission of HIV varied by sexual practice. In the beginning of this century, many physicians started to question if there was in fact any risk of HIV transmission at all during fully suppressive antiretroviral therapy. The Rakai data indicted risk of transmission to HIV negative serodifferent partners was strongly correlated with the viral load of the positive partner; and while only two small observational studies prospectively evaluated this question in the setting of fully suppressive cART, the absence of any documented case of transmission with suppressive ART gained attention. In 2008 the Swiss Federal Commission on AIDS related issues published what became rapidly known as the ‘Swiss statement’. Based on the absence of any reported case and on additional biological data supporting the observation, the commission decided that the evidence was strong enough to claim absence of any risk of sexual transmission in the setting of optimal cART use. The statement also made reference to other similar public health messages, such as non-transmission to household contacts, where the absence of evidence was the only basis for such statements. Furthermore, the publication of the Swiss statement raised the profile of this issue and likely supported the reporting of any observed cases of transmission. The continued absence of evidence of any such cases was a further argument supporting the statement of ‘no-risk’. The obvious weakness of the ‘Swiss statement’ was the assumed detection and reporting of cases of transmission. Therefore, the development of prospective, well-designed studies actively looking for cases of transmission in the setting of suppressive ART provided important scientific evidence to support the statement of ‘no-risk’. None of three large studies observed a single case of sexual transmission in the setting of fully suppressive cART. The increasing number of documented exposures without any signal of risk of transmission increases the certainty of the ‘no risk’ statement.