Timothy Cardinal Dolan, the archbishop of New York, departed for Rome on Tuesday to witness the pope's final public address before the latter officially resigns.
Then comes the start of the next chapter when Dolan and the other cardinals essentially cut themselves off from the outside world and go into conclave to begin the process of choosing the next leader of the Roman Catholic Church.
Pope Benedict XVI will make his final public appearance as Pontiff in St. Peter's Square on Wednesday.
The 150 cardinals will meet on Monday to discuss the start of the conclave and attend to some church business.
Pope Benedict changed the rules, allowing the cardinals to skip the traditional 15-day waiting period, and begin the conclave as soon as they want.
When it does get underway, the cardinals will be in virtual isolation in the Sistine Chapel.
Who emerges as the next pope is impossible to predict. But Dolan said he is fairly certain it won't be him.