In 1637, a priest and lawyer named Diego de Cisneros wrote to Philip IV, king of Spain (and as Philip III king of Portugal), whose combined empires stretched across the globe. Cisneros’s immediate concerns were in France, where he said that New Jews—the baptized descendents of Jewish converts to Christianity who had returned to Judaism—were plotting against Spanish interests “in all the provinces of the world.” Cisneros urged Philip IV to confront this threat, which he argued had its center in the synagogues of Amsterdam and Hamburg, but which reached to the Indies and beyond. This lecture uses the writings of Cisneros and others to investigate Spanish fears about New Jews and Judaizing New Christians as a distinctly global phenomenon. Writers like Cisneros were increasingly aware of the fragility of the Spanish empire in the 1630s. Furthermore, they identified the influence of New Jews and New Christians as a central cause of this weakness. For Cisneros and others, New Jews and New Christians were implacable religious enemies, powerful economic actors, and destabilizing political agents. To counter this threat, Cisneros and writers like him across the Iberian empires urged concerted action. Their influence is evident in a striking increase in the prosecution of Judaizers by inquisitorial tribunals in locations as disparate as Goa, Cartagena, Mexico, Toledo, and elsewhere during the 1630s and 1640s.