Iran and the United States have had no direct diplomatic relations since the 1979 storming of the US embassy in Tehran, when radical students held a group of American diplomats hostage for 444 days.
After a decade of stop-start talks, both sides have engaged seriously over the past year with the group of global powers, known as the P5+1, to hammer out a complex comprehensive nuclear agreement.
But the two nations have been driven to the negotiating table by their own agendas.
"If there is an agreement that prevents Iran from developing a nuclear weapons capability through diplomatic and peaceful means that's a major achievement for US diplomacy, and internationalism," said Alireza Nader, a senior policy analyst with the RAND Corporation.
As the world awaits the outcome of next week's all-out push in Vienna toward a November 24 deadline, Nader warned it was impossible to "read the tea leaves."
Like most observers, he says so much has been invested and the stakes are so high that the most likely scenario is the emergence of the contours of a deal with some last details still to be worked out.
A deal permanently removing the threat of a nuclear-armed Iran would be a stunning victory for Obama.
With just two years left of his second term, the Democrat is under fire at home and abroad for his perceived chaotic and timid foreign policy particularly in dealing with the chaos in the Middle East.
For Iranians, it could spell the lifting of a rigorous global sanctions regime that has crippled the country's economy.
But "if there is a deal, it won't make for friendship between Iran and its erstwhile antagonists," cautioned Mark Fitzpatrick, a former US State Department official focused on non-proliferation issues now at the International Institute for Strategic Studies in London.
"Friendship no, uneasy bedfellows yes," he said.
In Washington, any dealings with Iran are highly politically charged.
Many Republicans, who now control both chambers of Congress after elections earlier this month, have been infuriated by the tentative rapprochement of Obama, a Democrat, toward Iran.
They accuse the president of ignoring the existential fears of key regional ally Israel, which is vehemently opposed to any dealings with Iran.
And their anger was only further fueled by reports of a secret letter from Obama to Supreme Leader Ayatollah Ali Khamenei last month.
Republicans warn Obama is being fooled by the new, more moderate face of the Islamic republic, which aims to win billions of dollars in sanctions relief and will still covertly seek to develop a nuclear weapon.
Legislation is already pending before US lawmakers that instead of lifting sanctions would impose even harsher ones.
Such a move would be "naive, dangerous and not a viable option," said Kelsey Davenport, an analyst with the Arms Control Association.
"Further sanctions could push Iran away from the negotiating table and the US closer to a military strike."
But a political dustup is brewing, with Republicans claiming Obama is seeking to go behind their backs and use presidential authority to ease as many sanctions as he can without seeking congressional approval.
Meanwhile, any normalization of ties would also prove "harmful for the conservative establishment in Iran, because they need the United States as an enemy," Nader said.
"They're worried that if Iran opens up even more to the West that would undermine their basis of power."
Other key US allies such as Sunni Saudi Arabia have been wary of US moves to engage with Shia Iran.
But there are hopes among some that a nuclear deal may hold the key to unlocking channels to discuss other conflicts notably in Syria and Iraq.
US diplomats have acknowledged raising the issue of the Islamic State group, also known as ISIL, on the sidelines of the nuclear talks.
But they are taking a cautious approach.
Iran remains blacklisted by the US as a state sponsor of terror, and Washington has serious concerns about its human rights record.
"The US administration is quite wary of Iran's regional intentions and its behavior," said former top US diplomat on non-proliferation Robert Einhorn, now an expert with the Brookings Institution.
"While it recognizes that there are issues on which they share common interests, such as the defeat of ISIL, there are also areas in which their interests conflict such as on Syria."
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The Obama Administration is fooling its people & the world at large. The Iranian's have achieved the Enrichment of Uranium & will fool the world that it believes in rolling back its Nuclear Program.
The enemy of my enemy is my friend.