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The US President is due to give a 45-minute address at the Al-Azhar University in Cairo at 10.10GMT, in which he will talk candidly about issues that have caused tension between the United States and the Muslim world.
His audience will be listening carefully to see how far his views on Iraq and Afghanistan differ from those of his predecessor, George W. Bush, whose policies were deeply unpopular.
Mr Obama's choice of Cairo as a venue is intended to show his interest in building warmer relations in the Middle East. He has said repeatedly that he wants to encourage the fragile Arab-Israeli peace process.
The speech is a gamble that has already been written off by some. As Air Force One landed in Egypt this morning, Ayatollah Ali Khamenei, the supreme leader of Iran, said in a televised address that America was deeply hated in the Middle East and that only action, not slogans, could change that.
The Israeli newspaper Haaretz printed a cartoon today of Mr Obama wearing Arab headdress, captioned "Barack Hussein Obama the Anti-Semitic Jew-hater", which was being posted up around Jewish settlements this morning ahead of his speech.
Others seem keen to hear what Mr Obama has to say. "I really think it’s a big deal to people, that he’s coming here to Egypt rather than addressing the Muslim world from the White House," Haytham al-Akkad, 21, a university student, said. "People are anxious to hear what he’s got to say."
They are also clear about what they think he should say. The main messages Muslims want to hear is a clear statement of respect for their religion. They also want a tough, even-handed approach on the conflict between Israel and the Palestinians.
"If he wants to bridge the gap he must speak positively about Islam," Emad Gad, of the Al-Ahram Centre for Political and Strategic Studies, said. He noted that Mr Obama had already appeared on Arabic-language news channels talking about how his father and relatives in Kenya were Muslims, in an attempt to establish a bond with the man on the street.
He said that it was possible for Mr Obama to turn over a new leaf with the Arab world after almost a decade of mistrust with President Bush.
"You have to understand the Arab mentality. They are dealing with persons, not policies or countries. They put all the blame on the Bush Administration, and are dealing with Obama as a fresh president with a positive agenda," Mr Gad said.
As for the issue of the Palestinian conflict, many people in Cairo were pleased at the US administration’s tougher stance on Israel settlement building, which Washington has said must stop completely as part of renewed peace efforts.
"I hope he’ll get serious on the Palestine issue," said Yasmeen El Khoudairy, a 19-year from Gaza who is studying at the American University of Cairo. "He has to stop Binyamin Netanyahu."
Mr Netanyahu, the Israeli Prime Minister, refuses to endorse the idea of an independent Palestinian state and backs continued "natural growth" of the half-million settler population in the territories Israel conquered in 1967.
Most Middle East analysts agree that settling the decades-long dispute between Israel and the Palestinians would undercut the bitterness that fuels so much Islamic militancy. But many also want him to press authoritarian Arab regimes to allow more political freedom, justice and respect for human rights, another force that propels people towards violence.
Mr Obama’s visit yesterday to King Abdullah of Saudi Arabia, and his meeting today with Hosni Mubarak, Egypt’s long-term ruler, have prompted criticism that he will continue US backing of oil-rich states or those that stand up to Islamic militancy at the cost of human rights.
Few, however, thought that the US leader should push the Arab leaders publicly, a move that could backfire on the youthful president and make him appear naive.
"Democracy and human rights must be discussed behind closed doors, I think this will be more positive than speaking out," said one political analyst. He noted that any perceived slight to Mr Mubarak, who brooks no real opposition, could prompt the Egyptian leader to organise anti-American demonstrations or vilify America in the state-run press.
As Mr Obama headed into the region, one of Egypt’s most infamous sons, Al-Qaeda deputy leader Ayman al-Zawahiri, attempted to sour the US outreach to the Muslim world, accusing him of siding with the regimes in Saudi Arabia and Egypt.
"His bloody messages were received and are still being received by Muslims, and they will not be concealed by public relations campaigns or by farcical visits or elegant words," he said on an Islamist website.
"It is a clear message that America does not stand with reform and change and other lying American propaganda, but it stands with the continuation of the existing tyrannical, rotten regimes."
The Egyptian capital has been spruced up for Mr Obama's visit, with huge road-building machines busy repaving the tarmac and adding to the chaos of the city’s traffic. Bewildered commuters were last night left pondering how to get home after a bus station in the area was closed as police sealed off the centre for security sweeps.
Some Egyptians were pleased that at least their cracked and pitted roads were receiving a facelift, even if it was only to convince the American leader that things are better than they appear. They were also hoping that his speech will not be as cosmetic as the city’s last minute make-over.