The threat of terrorists of using nuclear material in a "dirty bomb" -- or even obtaining an atomic weapon -- has loomed large over the summit, punctuated by revelations that IS members tracked a Belgian nuclear scientist on video.
"ISIL has already used chemical weapons, including mustard gas, in Syria and Iraq," Obama said, using an acronym for the IS group.
"There is no doubt that if these madmen ever got their hands on a nuclear bomb or nuclear material, they most certainly would use it to continue to kill as many innocent people as possible."
Obama said about 2,000 tons of nuclear materials are stored around the world at civilian and military facilities, some of them not properly secured.
"Just the smallest amount of plutonium -- about the size of an apple -- would kill and injure hundreds of thousands of innocent people," he said.
"It would be a humanitarian, political, economic and environmental catastrophe with global ramifications for decades."
The nuclear security summit comes in the wake of attacks in Paris and Brussels that have killed dozens and exposed Europe's inability to thwart destabilising attacks or track Islamic State operatives returning from Iraq and Syria.
Though the summit is focused on fissile stockpiles, other nuclear concerns inevitably have drawn broad attention, including North Korea and its continued testing of nuclear devices and ballistic missiles.
The reclusive nation fired another short-range missile off its east coast today, the latest in a series of North Korean missile launches during what has been an extended period of military tension on the Korean peninsula.
In January, North Korea detonated a nuclear device -- its fourth such test -- and a month later launched a long-range rocket.
"We are united in our efforts to deter and defend against North Korean provocations," Obama said after meeting Japanese Prime Minister Shinzo Abe and South Korean President Park Geun-Hye.
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