There were two principle inquisition groups, one is Italy (Rome) and one in Spain (Seville). The Roman Inquisition is best known for putting Galileo on trial in 1633.

In 1545, the Spanish Inquisition created a list of European books considered heretical and forbidden in Spain. The Spanish Inquisition focused on the rising population of Spanish Protestants in the 1550s. In 1556, Philip II ascended the Spanish throne and Lutherans were hunted down and burned at the stake.

The machinery of the Inquisition was employed when the first signs of Protestantism appeared in Spain in the sixteenth century. Spain held the view that religious dissidence was a danger to social unity and peace, and was a revolt against lawful authority. Dread of the Spanish Inquisition spread to religious wars both in France and in the Netherlands.

In 1577 a nest of Protestants was discovered in Seville. Over a hundred arrests were made, chiefly of clergy, monks and nuns, of whom sixteen were subsequently burned. A further batch of thirty-three was sentenced to various penalties and nine were put to death. With this, the last spark of native Protestantism in Spain was virtually quenched. Thereafter, the Protestants who fell into the hands of the Spanish Inquisition were foreigners, mostly from Southern France.

In France, although the Edict of Nantes in 1598 concluded the fighting during Henry IV's reign, the political freedoms it granted to the Huguenots became an increasing source of trouble during the 17th century. The decision of King Louis XIII (1610-1643) to reintroduce Catholicism in a portion of southwestern France prompted a Huguenot revolt and 10% of the total population imigrated. By the Peace of Montpellier in 1622, the fortified Protestant towns were reduced to two, La Rochelle and Montauban. Another war followed. Under the 1629 Peace of La Rochelle, the authority of the Edict of Nantes was reduced, though Protestants retained some of their prewar religious freedom.

In 1661 Louis XIV, who was particularly hostile to the Huguenots, started assuming total control of his Catholic government. In 1681, he instituted a policy of intimidating Huguenot families to convert to Roman Catholicism or emigrate. In October 1685, Louis XIV revoked the Edict of Nantes altogether and made the practice of Protestantism illegal in France. Most Protestants chose to leave France rather than convert, with most moving to England, Prussia, the Dutch Republic, or Switzerland.