President Barack Obama hosts an international summit in Washington Thursday and Friday aimed at ensuring that nuclear material in the world's roughly 1,000 atomic facilities is secured.
Here is a breakdown of what's at stake:
Obama convened the first Nuclear Security Summit in 2010, followed by similar gatherings in Seoul in 2012 and The Hague in 2014.
The meetings focus on preventing criminals from accessing stockpiles of radioactive materials, reducing highly enriched uranium and separated plutonium, enhancing the detection of smuggling, and cybersecurity.
Considerable progress has been made, with several countries reducing or eliminating their stockpiles of nuclear material.
For example, Japan this month is returning to the United States enough plutonium to make 50 nuclear bombs.
But despite these advances, a January report by the Nuclear Threat Initiative (NTI), a leading US nonproliferation watchdog, found basic weaknesses persist in securing the world's fissile materials.
And according to a 2015 study by the International Panel on Fissile Materials, enough plutonium and highly enriched uranium stockpiles remain to make the equivalent of 200,000 weapons of the magnitude that leveled Hiroshima in 1945.
The fissile materials in question do not include state-owned nuclear weapons, leading critics to say the summits are not broad enough in scope.
"This is an important mission, but it's beneath the pay grade of the 50 or 60 heads of state that are going to convene in Washington," said Bruce Blair, co-founder of anti-nuclear group Global Zero.
"We should have an agenda ... that would cover all fissile materials, civilian and military."
Since the summits began, 14 nations have eliminated their fissile material stockpiles, and other countries have stepped up efforts to secure theirs.
But at the same time, other nations are ramping up their nuclear capabilities.
Countries like Pakistan, India and North Korea have built new bombs, and experts warn these fall behind in safety standards aimed at preventing accidental detonation.
The Islamic State group has already used chemical weapons, and experts fear the jihadists are trying to secure fissile material to make a "dirty bomb." Such a device is a regular bomb, but would explode radioactive material across an area.
Highlighting the risks, Belgian police investigating the November 13 Paris terror attacks found 10 hours of video of the comings and goings of a senior Belgian nuclear official.
One agenda item at the summit will see leaders discussing a hypothetical nuclear security crisis.
Next steps, possible outcomes
Sharon Squassoni, director and senior fellow at the Center for Strategic and International Studies' proliferation prevention program, said the latest summit aims to consolidate progress made so far, such as seeing countries that committed to certain actions implement these.
The 2014 summit saw 35 countries sign up to various pledges -- but key players including China, India, Russia and Pakistan did not join in.
"It would be really important for those countries to sign on," Squassoni said.
Other new commitments could include greater information exchange, or the opening up of facilities to inspection by peer nations or the International Atomic Energy Agency.
Given this is the last summit under Obama, a big question will be how nations can track progress in the future and whether the United States will continue to convene such meetings under its next president.