On one of Pope John Paul II's (search) last major trips four years ago, he stood in the ancient Omayyad Mosque in Syria and appealed for Christians and Muslims to seek common ground rather than confrontation.
"May the hearts of Christians and Muslims turn to one another with feelings of brotherhood and friendship," urged the pontiff, the first pope to enter a Muslim place of worship.
The words — spoken just four months before the Sept. 11, 2001, terrorist attacks — now stand a challenge for his successor. Just as the Cold War (search) defined the beginning of John Paul's 26-year papacy, the rifts between the West and Islam will likely influence how the next pope measures his priorities.
Free live streaming video of the pope's funeral at 4 a.m. EDT on FOXNews.com.
Relations with Islam — and who is best equipped to handle the delicate questions — is emerging as one of the factors that will shape the decision of the cardinals when they gather this month to pick the 265th pontiff.
"We have to learn to live with Islam," said Cardinal Theodore McCarrick (search) of Washington, speaking to reporters Tuesday in Rome. "We have to learn how to dialogue with Islam."
Chicago Cardinal Francis George added: "The history between Catholicism and Islam is not a happy one. We want to live at peace in a global society, so a dialogue with Islam is particularly important."
At least two cardinals could receive extra attention at the conclave in discussions about Islam (search).
Cardinal Francis Arinze of Nigeria has been based at the Vatican for decades, but spent his youth amid the country's mix of Christian and Muslims. The Vatican is also alarmed about inter-religious clashes in Nigeria that have claimed thousands of lives since the late 1990s. But Arinze would require a history-shaping act by the generally conservative College of Cardinals: naming the first African pope in modern times.
Cardinal Godfried Danneels of Belgium also is seen as having a deft diplomatic touch, but his liberal-minded views could alarm some conservative cardinals.
The concerns about Islam are particularly pressing to the 11 American cardinals who will join the conclave. Unlike Europe and elsewhere, there are few high-profile Muslim leaders in the United States to conduct serious interfaith contacts. The Vatican — as both a diplomatic entity and religious power — becomes an important forum for outreach.
The Holy See also sees more immediate worries in the rise of radical Islam.
Christians have been targeted by Muslim guerrillas in the Philippines, Iraq and elsewhere in recent years. The Vatican also has a stake in maintaining the sensitive religious balance in Jerusalem, where Christians often must carefully tread between the bigger forces of Judaism and Islam.
"The Christians are often between the hammer and the anvil," said Daniel Rossing, who heads a Jerusalem-based group that promotes inter-religious dialogue.
During the late pope's historic trip to Syria, he silently listened as Syria's President Bashar Assad denounced Jews for trying to "kill the principles of all religions." The Vatican refused to comment on the diatribe, apparently concerned any reaction would upset years of carefully crafted relations with the Muslim world.
The difficulty for the new pope is to further cultivate rapport with Muslims in the highly charged post-Sept. 11 politics.
"The new pope will have a different task ahead," said Daniel Thompson, director of religious studies at Fordham University in New York. "Who do you talk to? Who represents the Muslim population? How do you properly engage Islam with the contemporary situation?"
The new pontiff will inherit a reservoir of good will.
John Paul II received considerable praise in the Muslim world for his calls to end the Israeli-Palestinian conflict and his opposition to the U.S.-led war in Iraq. The outpouring following his death Saturday reflected his standing — and the challenges for the next pontiff to even approach the achievements.
"Muslims and Christians alike have lost the pope," said Syria's prominent Islamic cleric, Sheik Salah Keftaro.
The pope's death "is a big loss for the Catholic Church and the Islamic world," said Sheik Sayed Tantawi, the head of Egypt's Al-Azhar, Sunni Islam's most prestigious center of learning.
The list of dignitaries from the Islamic world for the pope's funeral on Friday is already impressive and continues to grow: Syria's Assad, President Mohammad Khatami of Iran and Religious Minister Alwi Shihab of Indonesia, the world's most populous Muslim nation.