One of the most ancient and distinguished families of the Roman nobility, supporters of the papacy and the Guelphs against the emperor and the Ghibellines, whose cause was ordinarily advocated by the great Colonna family of Rome. The wars between the Orsini and the Colonna form an important part of medieval Italian history. In addition to three popes – Celestine III, Nicholas III, and Benedict XIII – the Orsini have given many distinguished members to Church and State including
- Cardinal Matteo Rosso (died c.1305), imprisoned at the instance of the French party at the conclave of Viterbo to secure the election of Martin IV. Later he supported Pope Boniface VIII against Philip the Fair.
- Cardinal Napoleone (1263–1342), a friend of the Franciscan Spirituals and supporter of Louis of Bavaria against the papacy.
- Cardinal Giordano (died 1438), deserted Pope Gregory XII, and later acted as legate of Martin V in an effort to make peace between England and France. He upheld the rights of the pope at the Council of Basle, and left a valuable diary relating to that council.
- Cardinal Latino (1411–1477), commanded the papal fleet against the Turks.
- Cardinal Alessandro (1592–1626), renowned for his asceticism and heroic charity, would have bcome a Jesuit but for the prohibition of Pope Gregory XV. He was patron of Galileo.
- Fulvio (1529–1600) was noted as a historian, humanist, and archaeologist.
The ancient family of Roman Orsini is extinct; the present Roman princes descend from a Neapolitan branch, and their head always enjoys the dignity of assistant at the papal throne.