Moving from the historiographical debate on the relationship between the radical religious dissent of the 16th century on one side, and the libertinage and the deism on the other side, the paper aims to propose a new interpretation, different from the traditional one. Classical and current paradigms deny every type of relationship between the libertines, the deists and religious dissent. But by taking as a case study the Italian Reformation’s most radical movements, the paper suggests a conceptual continuity (although not without changes) between the claims of radical religious movements and some of the most extreme libertine and deistic ideas. And it shows how the movement of ‘eretici italiani del Cinquecento’ played a crucial role in the genealogy of modern Western culture.