Speaking about the first centuries of inquisition (the 'medieval inquisition'), from 1220's through the 14th century, the inquisitors came from 2 sources: bishops and Dominican friars. The inquisitions at this time were not an institution, they were individual assignments run and managed locally but directly reporting to the pope.

These first inquisitions were held in the south west of modern-day France, in cities and large towns such as Toulouse, Narbonne, Albi, Perpignan, Carcassonne, Agen, Montauban.

The fact that inquisitions were run by local bishops and/or Dominicans was cause for no small amount of trouble, and in fact there were protests back and forth between bishops and Dominicans and the pope about matters of efficacy, control and jurisdiction. Toulouse in particular during the 1240s was the scene for Dominicans being chased out of the city by some of the local populace, possibly with the interference of the bishop.

The Dominican Friars came to the role of inquisitors quite 'naturally': they were often exceptionally bright, well trained by Paris universities in theology. The order was created and seated in Toulouse as a reaction to the 'heresies' of local apostolic, traveling unlicensed preachers. The order of mendicant preachers was named for Dominic Guzman who pleaded with Pope Innocent III in 1205 to permit him to wander the country side of south west France preaching against heresy: such traveling friars had never been licensed before, but it was one of the attempts of the papacy to counter heresy in Occitania before the Albigensian Crusades.

The Dominicans, as a sharp, intellectual, experienced apostolic order were well trained and well placed to handle the inquisition, and over the next century they drafted many manuals, refined techniques, and expanded the base of operations and expanded the targets of heretical thought.

At the same time bishops were also conducting inquisitions. One of the most famous medieval inquisitions, that of the muti-decade interrogation of the Pyrenean village of Montaillou, was conducted by Bishop Jacques Fournier of the bishopric of Pamiers; he eventually became Pope Benedict XII.

The subsequent Roman Inquisition in Italy was created by the papacy in the 16th century, with panels composed of cardinals or papal legates and Dominicans. The Spanish Inquisition was created in the renaissance as a political institution with inquisitors appointed by secular authority; the inquisitorial team was drawn from lawyers and lay clergy (not from holy orders).

Inquisitions carried the same name, but they were different entities composed differently.