Wednesday's meeting between President Bush and Pope Benedict XVI is the 25th between a pope and a sitting president, and only the second at the White House.
And, as CBS News Senior White House Correspondent Bill Plante points out, it may seem hard to imagine today but, for much of the nation's history, the idea of a president welcoming a pope to 1600 Pennsylvania Avenue would have been "nothing short of shocking."
"Catholicism was an outsider to the culture for a long time," explains Georgetown University Amaturo Chair in Catholic Studies Chester Gillis. "And only in the last 50 years or so has (Catholicism) really been ingrained in the culture deeply."
The first papal-presidential get-together came shortly after the end of World War I, when Woodrow Wilson was received at the Vatican by Pope Benedict XV in 1919. The next came 40 years later, when President Eisenhower saw Pope John XXIII in Rome.
President Carter hosted the first White House visit by a pope, when John Paul II came on Oct. 6, 1979.
Since then, every president has met with the pope at least once, and often more.
President Bush is the Oval Office-holder to do it the most, with five meetings with two popes.
Back in 1928, the fear of Vatican influence in the U.S. was still strong enough to sink New York Gov. Al Smith, the first Catholic to run for president.
Gillis says a joke at the time had it that, "The day after the election he lost so badly, (Smith) sent a one-word telegram to the pope: 'Unpack.' "
U.S.-Vatican relations were strained during World War II by the pope's determination to remain impartial.
The 1959 meeting between Dwight Eisenhower and John XXIII was followed a few months later by Catholic candidate John F. Kennedy taking on fears about his faith in a historic speech, saying, "I am not the Catholic candidate for president. I am the Democratic Party's candidate for president, who happens also to be a Catholic.
The post-Eisenhower meetings of presidents and popes happened for reasons Plante calls "both high-minded and practical."
"It could make a whole difference in electoral votes by bringing out the so-called Catholic vote," observes CBS News consultant Douglas Brinkley.
The first pope to visit the U.S. was Paul VI, who gave an address at the United Nations in 1965 pleading for peace.
It took another 14 years for a full-scale papal tour of the U.S. -- the first of many for John Paul II. It included his historic White House stop.
As rulers of Vatican City, popes are heads of state, but the U.S. didn't have formal diplomatic relations with the Vatican until 1984, when President Reagan perceived the anti-Communist Polish pope as a partner.
Says Brinkley, "They saw, with Pope John Paul II in power, a chance to win the Cold War through a kind of Vatican-U.S. government alliance."
The charismatic John Paul had 15 meetings with presidents from Carter to the current Bush, six of them on American. soil.
The closer relationship benefits the Vatican, Plante says, by giving it the chance to lay out its agenda to the world's most powerful leader, the president of the United States.
"Whether or not that hearing translates into policy or action is another question," notes Gillis, "and I think, frequently, it really doesn't."
Mr. Bush and Pope Benedict will agree on some things, Plante adds, such as opposition to fetal stem cell research, abortion, and same sex marriage, but disagree on others, such as the death penalty and the trade embargo on Cuba.
This pope has oppose the Iraq War, but the Vatican is more concerned now with protecting what remains of the Christian community there -- making it stable and safe -- than anything else, Plante concludes.