Born in Medellín, Colombia, Castrillón Hoyos attended the seminaries in Antioquia and Santa Rosa de Osos before studying at the Pontifical Gregorian University in Rome.

After becoming an official in the diocesan curia of Santa Rosa de Osos, Castrillón was made director of radiophonic schools.

[1][2] Castrillón Hoyos also served as Secretary General (1983–1987) and President (1987–1991) of the Latin American Episcopal Conference, where he opposed liberation theology, which many of his colleagues supported.

On 26 October of that same year he served as papal envoy to the signing of the peace accord between Peru and Ecuador to settle their border dispute.

On 14 April 2000, he replaced Angelo Felici as President of the Pontifical Commission Ecclesia Dei, the office that handles the Holy See's relations with traditionalist groups such as the Society of St. Pius X. Castrillón was appointed Grand Prior of the Sacred Military Constantinian Order of Saint George by Infante Carlos, Duke of Calabria on 27 February 2004.

[citation needed] Following the death of John Paul II, Castrillón participated in the 2005 papal conclave and was himself considered papabile, a possible successor to the papacy.

[4] In January 2009, while Castrillón still headed the Pontifical Commission, Pope Benedict lifted the excommunications several bishops of the Society of St. Pius X (SSPX), including Richard Williamson, who was later identified a Holocaust denier.

"[10] When Castrillón's letter to Pican became public in 2010, Vatican spokesman Federico Lombardi said it showed how important it was to centralize handling of Catholic sex abuse cases by clerics under the Congregation for the Doctrine of the Faith.

[12] While indicating that his Congregation was still studying the question, Castrillón wrote that some of the Irish bishops' proposals "appear contrary to canonical discipline", which could lead to actions being overturned if an appeal were made to a higher level.

The documentary's depiction of resistance the Irish bishops experienced from Castrillón put them in a more favorable light at a time when they, and especially Archbishop Desmond Connell, were the target of savage criticism.

In 2001, Ratzinger persuaded Pope John Paul II to make it mandatory to report all complaints of clerical sexual abuse to the Congregation for the Doctrine of the Faith.