The challenge of the negotiations has in no small part been made more difficult by the fact that the U.S. and Iran have had no formal, direct diplomatic relations since the 1979 Iranian Revolution that deposed the Western-friendly shah.
Iran's nuclear program first garnered serious attention in 2002. The fear that they would develop nuclear weapons, bringing a whole new arms race to the already-volatile Mideast, immediately brought international negotiators to Tehran.
Eventually, the U.S., along with France, Britain, Germany, Russia, and China, would produce an accord with Iran, but not before lots of starts and stops along the way.
The following is a timeline of how they reached an agreement.
June 2003 - Britain, France and Germany engage Iran in nuclear negotiations. Washington refuses to join.
October 2003 - Iran suspends uranium enrichment. At the same time, war in neighboring Iraq, and the repeated accusations by U.S. officials that the Islamic Republic was aiding Shiite militias fighting Americans, make relations between the two countries worse.
February 2006 - Iran announces it will restart uranium enrichment following the election of hardline president Mahmoud Ahmadinejad, a critical Iran report by the IAEA to the U.N. Security Council, and after Britain, France and Germany walk out of stalled negotiations. The Islamic Republic had said at the time they were working on a proposal with Russia to move its uranium enrichment program there, but details were never worked out.
June 2006 - The United States, Russia and China join Britain, France and Germany to form the P5+1 group of nations trying to persuade Iran to curb its nuclear program. Washington initially stays away from the negotiating table. Sanctions are proposed.
December 2006 - The U.N. Security Council imposes the first set of sanctions on Iran, banning the sale of sensitive nuclear technology. Russia and China, as they will throughout most of the negotiating process, favor less severe measures. Five more Security Council resolutions are passed by 2010, tightening the sanctions vise on the Islamic Republic.
July 2008 - Under President George W. Bush, the United States joins the nuclear talks for the first time.
The Ahmadinejad Era
September 2009 - The United States, the United Kingdom, and France present detailed evidence demonstrating that Iran has spent several years digging a covert enrichment site into a mountain, escalating concerns because the facility may be impervious to air attack. Iran acknowledges the existence of the facility, but insists it serves no military purpose. Speaking at an overflowing news conference, Ahmadinejad dodged a question about whether Iran had sufficient enriched uranium to manufacture a nuclear weapon, but said Tehran rejects such armaments as "inhumane."
October 2009 - Under President Barack Obama, a senior U.S. diplomat meets one-on-one with Iran's top nuclear negotiator. The talks are some of the most extensive between Washington and Tehran in three decades. Then-Secretary of State Hillary Clinton calls the current round of talks a productive session that has opened the door to a positive outcome. Many diplomats, however, say privately they have modest expectations for success.
February 2010 - Iran announces it has started to enrich uranium to near 20 percent, a technical step away from weapons-grade material. At this point, the Islamic Republic has defied five U.N. Security Council resolutions - and three sets of U.N. sanctions - and continued to grow its nuclear program.
January 2011 - Negotiations between Iran and the six world powers break off for what proves a 15-month hiatus. Iran refuses to make deep cuts in its nuclear program.
November 2011 - The IAEA outlines the possible military dimension to Iran's nuclear activities, saying some of the work being done is "specific to nuclear weapons." The U.N. atomic agency said the Islamic Republic had secretly obtained equipment and design information related to nuclear weapons, conducted detonator development, and attempted to figure out how to load a nuclear payload onto its Shahab 3 intermediate-range missile -- a weapon that can reach Israel, Iran's arch foe. Iran denies the allegations, saying they're based on falsified Israeli and U.S. evidence.
January 2012 - The IAEA says Iran is enriching to 20 percent at its mountain facility near Fordo. The European Union freezes the assets of Iran's central bank and halts Iranian oil imports. President Ahmadinejad then announces the country is ready to restart negotiations.
February 2012 - Supreme Leader Ayatollah Ali Khamenei publicly declares his country's nuclear program is peaceful. Khamenei, who has final say on all state matter in Iran, also said that Western powers know "we are not seeking nuclear weapons because the Islamic Republic of Iran considers possession of nuclear weapons a sin ... and believes that holding such weapons is useless, harmful and dangerous."
September 2012 - Israeli Prime Minister Benjamin Netanyahu delivers his famous "red line" speech at the U.N. General Assembly. In the speech, which featured a cartoon bomb drawing and Netanyahu wielding a red marker, Netanyahu insisted that Iran's nuclear program could have bomb-making capabilities by mid to late 2013. Many feared it was a warning that Israel was preparing to strike Iran directly.
September 2013 - Rouhani and Mr. Obama speak by telephone, the highest-level exchange between the two countries since Iran's 1979 Islamic Revolution. President Obama says afterwards the phone call led him to believe "we can reach a comprehensive solution." U.S. Secretary of State John Kerry and Iranian Foreign Minister Mohammad Javad Zarif begin their diplomatic exchanges.
November 2013 - Iran and the six powers announce an interim agreement that temporarily curbs Tehran's nuclear program and unfreezes some Iranian assets. The deal sets the stage for extended negotiations on a comprehensive nuclear accord.