The Inquisition was a permanent institution in the Catholic Church charged with the eradication of heresies. Unlike many other religions (e.g., Buddhism, Judaism), the Catholic Church has a hierarchical structure with a central bureaucracy. In the early years of the church, there were several competing sects that called themselves Christian. But after the Emperor Constantine I (280?-337 CE) made Christianity the state religion of the Roman Empire and the local administrative structures were pulled together into one hierarchy centered in Rome, doctrinal arguments were settled by Church Councils, beginning with the Council of Nicea in 325 (which formulated the Nicean Creed). Those whose beliefs or practices deviated sufficiently from the orthodoxy of the councils now became the objects of efforts to bring them into the fold. Resistance often led to persecution.

Heresies (from L. haeresis, sect, school of belief) were a problem for the Church from the beginning. In the early centuries there were the Arians and Manicheans; in the Middle Ages there were the Cathari and Waldenses; and in the Renaissance there were the Hussites, Lutherans, Calvinists, and Rosicrucians. Efforts to suppress heresies were initially ad hoc. But in the Middle Ages a permanent structure came into being to deal with the problem. Beginning in the 12th century, Church Councils required secular rulers to prosecute heretics. In 1231, Pope Gregory IX published a decree which called for life imprisonment with salutary penance for the heretic who had confessed and repented and capital punishment for those who persisted. The secular authorities were to carry out the execution. Pope Gregory relieved the bishops and archbishops of this obligation, and made it the duty of the Dominican Order, though many inquisitors were members of other orders or of the secular clergy. By the end of the decade the Inquisition had become a general institution in all lands under the purview of the Pope. By the end of the 13th centuries the Inquisition in each region had a bureaucracy to help in its function.

The judge, or inquisitor, could bring suit against anyone. The accused had to testify against himself/herself and not have the right to face and question his/her accuser. It was acceptable to take testimony from criminals, persons of bad reputation, excommunicated people, and heretics. The accused did not have right to counsel, and blood relationship did not exempt one from the duty to testify against the accused. Sentences could not be appealed Sometimes inquisitors interrogated entire populations in their jurisdiction. The inquisitor questioned the accused in the presence of at least two witnesses. The accused was given a summary of the charges and had to take an oath to tell the truth. Various means were used to get the cooperation of the accused. Although there was no tradition of torture in Christian canon law, this method came into use by the middle of the 13th century. The findings of the Inquisition were read before a large audience; the penitents abjured on their knees with one hand on a bible held by the inquisitor. Penalties went from visits to churches, pilgrimages, and wearing the cross of infamy to imprisonment (usually for life but the sentences were often commuted) and (if the accused would not abjure) death. Death was by burning at the stake, and it was carried out by the secular authorities. In some serious cases when the accused had died before proceedings could be instituted, his or her remains could be exhumed and burned. Death or life imprisonment was always accompanied by the confiscation of all the accused's property.

Abuses by local Inquisitions early on led to reform and regulation by Rome, and in the 14th century intervention by secular authorities became common. At the end of the 15th century, under Ferdinand and Isabel, the Spanish inquisition became independent of Rome. In its dealings with converted Moslems and Jews and also illuminists, the Spanish Inquisition with its notorious autos-da-fe represents a dark chapter in the history of the Inquisition. In northern Europe the Inquisition was considerably more benign: in England it was never instituted, and in the Scandinavian countries it had hardly any impact.

Pope Paul III established, in 1542, a permanent congregation staffed with cardinals and other officials, whose task it was to maintain and defend the integrity of the faith and to examine and proscribe errors and false doctrines. This body, the Congregation of the Holy Office, now called the Congregation for the Doctrine of the Faith, part of the Roman Curia, became the supervisory body of local Inquisitions. The Pope himself holds the title of prefect but never exercises this office. Instead, he appoints one of the cardinals to preside over the meetings. There are usually ten other cardinals on the Congregation, as well as a prelate and two assistants all chosen from the Dominican order. The Holy Office also has an international group of consultants, experienced scholars of theology and canon law, who advise it on specific questions. In 1616 these consultants gave their assessment of the propositions that the Sun is immobile and at the center of the universe and that the Earth moves around it, judging both to be "foolish and absurd in philosophy," and the first to be "formally heretical" and the second "at least erroneous in faith" in theology. This assessment led to Copernicus's De Revolutionibus Orbium Coelestium to be placed on the Index of Forbidden Books, until revised and Galileo to be admonished about his Copernicanism. It was this same body in 1633 that tried Galileo.