The Secretary of State of His Holiness, known as the Cardinal Secretary of State, presides over the Holy See's Secretariat of State, which is the oldest and most important dicastery of the Roman Curia. The Secretariat of State performs all the political and diplomatic functions of the Holy See and the Vatican City State. The secretary of state is sometimes described as the prime minister of the Holy See, even though the nominal head of government of Vatican City is the President of the Pontifical Commission for Vatican City State.

The Holy See, also called the See of Rome, Petrine See or Apostolic See, is the jurisdiction of the pope in his role as the Bishop of Rome. It includes the apostolic episcopal see of the Diocese of Rome, which has ecclesiastical jurisdiction over the worldwide Catholic Church and sovereignty over the city-state known as the Vatican City. As the supreme body of government of the Catholic Church, the Holy See enjoys the status of a sovereign juridical entity under international law.