The US president has set himself the mission of convincing fellow leaders from 45 nations that they faced the same threat and to establish a plan to secure every ounce of the world's nuclear weapons-grade fuel.
"The single biggest threat to US security, both short-term, medium-term and long-term, would be the possibility of a terrorist organisation obtaining a nuclear weapon," Mr Obama said. "This is something that could change the security landscape in this country and around the world for years to come."
"If there was ever a detonation in New York City, or London, or Johannesburg, the ramifications economically, politically and from a security perspective would be devastating."We know that organisations like al-Qaeda are in the process of trying to secure nuclear weapons or other weapons of mass destruction, and would have no compunction at using them."
Discussions at the two summit which ends on Tuesday are focusing on stocks of separated plutonium and enriched uranium which could be used by extremists to manufacture weapons.
They are part of an initiative by Mr Obama to eventually rid the world of nuclear weapons by controlling "loose nukes", reducing the US military's strategic dependence on nuclear arms and halting proliferation.
It was this vision that earned him the 2009 Nobel Peace Prize and accompanying criticism that he had done little to deserve the award.
Washington and Moscow have made substantial progress since the collapse of the Soviet Union to secure the greatest single supply of highly enriched uranium, but sufficient supplies remain scattered around the world to make thousands of bombs.
For many Western officials and experts, nuclear-armed Pakistan remains the main concern because of its instability and the proximity of the Taliban and al-Qaeda bases in the country's tribal areas to nuclear locations.
"For my money Pakistan is the most dangerous country on Earth," said Joseph Cirincione, president of the Ploughshares Fund, a Washington foundation promoting non-proliferation.