While Pope Benedict XVI might be the first Holy Father to voluntarily resign because of old age and deteriorating health, the papacy has a long history of health ailments -- from depression to gout to cancer.
According to church law, as long as a pope is able to conduct Mass, he can continue to do so – even if he is suffering the pain of failing kidneys and is otherwise bedridden, like Pope Alexander VII was in 1667.
Pope Alexander VII's surgeon and confessor tried to persuade him not to go before the crowd on Easter Sunday of 1667, but he did it anyway. The pope died three days later, according to "The Deaths of the Popes," by Wendy J. Reardon.
More than a century later, Pope Clement XIV complained of pain and wasting away before he became known as the pope who drooled and had eyes that "darted in their bulging sockets" as he fearfully clung to walls for fear of a Jesuit assassination attempt, according to Reardon. He died after correctly predicting his own death in 1774.
Then, in 1958, Pope Pius XII died after enduring hiccoughs and strokes for five years. The hiccoughs became so intense, that they tore the lining of his stomach, Reardon wrote. He died of complications from pneumonia at 82 years old.
Still, the popes stayed the course until their deaths.
"Death has never been an issue that has worried popes," said papal historian Anura Guruge, a former IBM employee who's spent the last six years researching the papacy and entering related data into more than 70 spreadsheets for some first-of-its-kind analysis. He's written two books on the subject.
"Popes talk about no purgatory for popes," he said. "They immediately go to God's house and they're immediately in the presence of the father. Many of the popes on their death beds expressed enormous amounts of joy."
With only seven voluntary resignations out of more than 265 legitimate popes, ailing and death have become part of the process, Guruge said. If God is ready for a new pope, he will simply call the current one home to heaven.
"This pope's resigning is essentially overriding God's will," he said, adding that Pope Benedict XVI's resignation was a surprise to him. "We had suspected that he had more health issues than had been made public. ... A pope resigning is really not the right thing to do."
Pope Benedict XVI, who was one of the oldest popes when he was elected in 2005 at age 78, had a stroke in 1991 that reportedly temporarily affected his vision. He fell in 1992 and 2009, and also had either arthritis or arthrosis, a similarly painful and debilitating joint condition. He was spotted using a cane during trips to Mexico and Cuba last year. He also used a mobile platform to get around St. Peter's.
The pope's brother, George Ratzinger, told the U.K.'s Telegraph that the pope's doctor advised him against taking any more transatlantic trips.
"His age is weighing on him," Ratzinger, 89, told the Telegraph, adding that the pope had been considering stepping down. "At this age, my brother wants more rest."
Father Virgilio Elizondo, a professor at the University of Notre Dame in Indiana, said he thinks Pope Benedict XVI made a very difficult but wise decision by resigning. He added that the papacy has a history of unpredictability, and the surprise resignation fits right in.
"I think when you consider the sincerity of the man, when you consider the weight of the universal church, and the greatest variety of issues affecting the church and the rest of the world, I could see how he could come to that decision," Elizondo told ABCNews.com."What's really needed is a younger person with more vigor and up-to-date knowledge about what's happening. I think that's the rationality behind this pope."
Pope Benedict XVI was just 73 days away from being the third oldest pope, but he will remain the fourth oldest pope because his resignation date is scheduled for Feb. 28, said Guruge. The three older popes were Pope Clement X, who lived to be just over 86 years old; Pope Clement XII, who lived to be 87; and Pope Leo XIII, who lived to be 93. They all died without resigning.
Pope Leo III, who died in 1903, became known as the "eternal pope" because he kept on living, Guruge said. Then, however, the job was less demanding because the pope didn't have to be on television or travel -- or tweet.
Although church law says that cardinals should submit their resignations to the pope when they reach 75 years old, there is no such law for the pope, said Father Francis Schussler Fiorenza, who teaches Roman Catholic theological studies at Harvard University. Fiorenza studied under Pope Benedict XVI about 40 years ago in Munster, Germany, when the pope was still Father Joseph Ratzinger.
"I know what he looked like when he was really young and healthy," Fiorenza told ABCNews.com, adding that Pope Benedict XVI's predecessor, Pope John Paul II, was sick until he died in 2005 at 85 years old.
Pope John Paul II lived with Parkinson 's disease for decades, but he died of cardio-circular failure and septic shock on April 2, 2005. He also had kidney failure.
New York Cardinal Timothy Dolan told ABC News that he trusts Pope Benedict XVI's judgment on stepping down, but he was impressed with the 85-year-old's ability to stay awake during a church leaders' meeting.
"I was amazed. He was there every day. Never fell asleep," Dolan said with a laugh. "I can't say that about myself in some of the talks."