The general consensus is that the treaty will eventually be ratified by the end of the year, but the issue is likely to be the subject of a heated political debate for much longer.
"He has a political opposition that's willing to use these reasonable but actually quite modest steps forward as political ammunition, and they widely misconstrue them to make cheap political shots," Sokolsi said. "If your political opposition is willing to exploit that, it's a tough battle to fight."
Even before the summit got off the ground, tensions were evident. On Thursday, Israel said Prime Minister Benjamin Netanyahu would not be attending, reportedly because of suggestions that some attendees would use the summit to criticize its nuclear program.
The fact that one of the United States' closest allies will not be in attendance is likely to put pressure on the United States.
"In practical terms, it may not have a lot of significance," said Christopher Ford, director for the Center for Technology and Global Security at the Hudson Institute, and a former special representative for nuclear nonproliferation in the Bush administration. But, "politically, it's not a good thing to call a giant international conference to show world unanimity and have that unanimity be so chopped away before the opening gavel."
Ford said the summit is a good way to bring together different world leaders to discuss a common threat, but what it means to achieve remains blurry.
"It seems to be in a large part a consciousness-raising exercise. Those are not bad, but they are not things that haven't been worked on in the past either," he said. "It strikes me as a lot of effort for a not of lot of payoff. ... People will have to get a whole lot more serious than saying nice things at a summit."
Iran will likely to be at the top of the president's agenda during the summit. The country's president, Mahmoud Ahmedinejad, only mocked Obama after the U.S.-Russia treaty, despite warnings of sanctions against it. Just on Friday, Iran unveiled what it called its third generation of centrifuges for nuclear enrichment.
"If Iran decides to acquire and deploy a nuclear weapon then you're likely to see a cascade effect where other countries will think they might have to exercise a nuclear option, including perhaps Saudi Arabia, Egypt, Turkey and others in the region," said former ambassador Richard Burt, who was the negotiator for the first Strategic Arms Reduction Treaty. "That would be in my view ... be a show stopper."
Others said the summit should avoid focusing solely on Iran but emphasize more how countries can come together to establish global standards.
"I don't think this should be turned into an Iran-bashing situation," said Oelrich, who believes Iran is a long way from becoming a nuclear power. "One of the things that we'll try to do is ... establish new international norms -- what is acceptable behavior, should nuclear weapons be legitimate instruments of national power."
Obama is bringing up the nuclear agenda at a time when very few Americans tend to think about it as a global threat. Barely half of Americans see nuclear terrorism as a top-level threat and most doubt a two-day summit of world leaders in Washington will do much to address it. Just 12 percent of Americans in a new ABC News/Washington Post poll called the chance that terrorists could obtain nuclear weapons "the single biggest threat the world faces."