Derived from the Latin infidelis, meaning “unbelieving” or “unfaithful,” the term was used by the Catholic Church during the Middle Ages (500–1350) to describe a threat posed by Muslims. As the Moors (Muslims from North Africa) moved into Spain early in the eighth century and the Seljuk Turks conquered much of Asia Minor during the eleventh century, medieval Christians (of which there were a growing number) became increasingly fearful of growing Muslim influence. Not only were people of the Islamic faith occupying lands that were formerly Christian, they soon prevented Christian pilgrims from entering their Holy Land in the Middle East.

The church responded to the so-called infidels by inspiring western Europeans to take up arms in the Crusades, which began in 1095 and ended unsuccessfully in 1291. In another effort to drive back Muslim expansion, in 1231 Pope Gregory IX (c. 1170–1241) issued a papal bull creating the Inquisition, the system by which heretics were discovered and punished. Many of them were burned at the stake.

The Moorish dominance of the Iberian Peninsula (present-day Spain and Portugal) lasted hundreds of years before the North Africans were driven out by armies of the Christian states. Thereafter, during the reign of King Ferdinand and Queen Isabella, Spain embarked on a period of profound suspicion. It conducted the Spanish Inquisition, by which anyone thought to be an infidel (the definition now broadened to include Jews) was discovered and punished.