In the 15th century there was considerable hostility towards the Jews throughout Europe. This was especially true in Spain. In 1492, seeking to consolidate their power and free themselves from the Vatican, King Ferdinand II and Queen Isabella of Spain turned to the Dominican priest Tomas de Torquemada, who proposed an Inquisition in 1483.

In 1492, the Spanish forced the surrender of the Muslim kingdom of Granada. The surrender of the city of Granada placed yet another large Jewish population under their rule. Tomas de Torquemada was appointed Inquisitor General and in 1492 became one of the main supporters of the Alhambra Decree that ordered all remaining Jews to leave Spain. As a result, large numbers of Jews converted to Christianity.

Ferdinand II pressured pope Sixtus IV to agree to let him set up an Inquisition controlled by the monarchy by threatening to withdraw military support at a time when the Turks were a threat to Rome. Sixtus IV initially agreed to the Spanish Inquisition but later described it as being overzealous. He issued a bull to stop it but after coming under increased pressure, withdrew it.

During the 16th century the Spanish Inquisition began to target Protestants. About 100 were burned as heretics. An index of prohibited books was drawn up that were alleged to contain heresy. The procedures would start with Edicts of Grace, where people were invited to step forward to confess heresy freely and to denounce others. If the prisoner refused to confess, torture was used. Sentences varied from fines to execution. The Spanish Inquisition was less active in the 18th century and it was definitively abolished on 15th July, 1834. It is estimated that between 3,500 and 5,500 people were executed between 1476 to 1834.