The conclave is a highly secretive and symbolic tradition that dates back more than a thousand years. The 115 cardinals will go into complete seclusion until a two-thirds majority elects the next pope. That's when we'll see the infamous white smoke billowing from a chimney atop the Sistine Chapel.
University of Dayton Relgious Studies Professor Sandra Yocum estimates the conclave will last three to five days.
"Most people are not anticipating it'll be on the first ballot," she said.
The cardinals have been discussing the church's future leader for a week. Many want the next pontiff to better unite congregations, communicate more with the public and media, and harshly address the sex abuse scandal to help the church overcome an era of negativity.
"They will need someone to deal with that. I also think they need someone who will be an effective administrator. Even Pope Benedict would say that was not his strong suite," Yocum said.
Cardinals from Sao Paulo, Brazil; Milan, Italy, and Boston have emerged as the top picks. Keep in mind, there has never been an American pope.
"This is a historic event in itself. It's been years since someone has stepped down from a powerful and important position so I hope everyone takes it seriously," said Aimee Madgler of Dayton.
"Given the turmoil the world, I think it's important we get someone with a good international perspective," Charlie Russo of Dayton said.
Cardinals can't vote for themselves and they aren't allowed to campaign for the papacy.