Born in the province of Caserta in 1943, he has been ordained priest in 1967.
In 1972 he has entered in the diplomatic service of the Santa Sede, missioned to the Papal Representation in Brazil, where he has worked in the service of the Church and of the poor till 1975.
Returned to Rome to the Secretariat of State, he has been nominated in 1987 as assessor for the General Affairs.
In 1992 he has been nominated archbishop and secretary of the Congregation for the Clergy and later on General Secretary of the Jubilee of the year 2000.
In February 2001 he has been elevated to the rank of cardinal by John Paul II, and has become Decan of the Congregation for the Evangelization of the People.
He has been in charge of the Papal Urbaniana University and member of Papal Councils and Vatican Congregations.
In May 2006 Pope Benedict XVI has nominated him Archbishop of Naples, where he has distinguished himself for his passionate pastoral work.
He has accommodated in 2007 the XXI edition of the “International Meeting Men and Religions for Peace”. Within that historical encounter with the title “For a world without violence” we remember the visit from the Pope to the city and to the representatives of the world-wide religions who had come to Naples, and the moving ceremony of the gift to the ecumenical Patriarchy of Constantinople of the relics of the apostle Andrew conserved until then in the Dome of Amalfi.
Cardinal Sepe said at the conclusion of the Meeting in Naples: “I would like that this event would not be at its end, but that it be as a child born here in Naples which can become the continuation of this spirit, the spirit of Naples”. Other fruit of his love for the dialogue is his recent visit rendered to the orthodox Patriarch Alexis II. In the course of this visit, he has delivered a personal message from Benedict XVI to the Patriarch.