The new treaty aims to slash the US and Russian nuclear arsenals
The Russian and American presidents have signed a long-awaited nuclear weapons pact in the Czech capital that will replace the 1991 Strategic Arms Reduction Treaty (Start).
The new treaty marks a milestone in the arms control process, as the BBC's Diplomatic Correspondent Jonathan Marcus reports from Prague.
This is really the first proper nuclear arms reduction treaty of the post-Cold War era.
It scales back the US and Russian nuclear arsenals - though by how much is an interesting point which I will come to in a moment.
New Start: 1,550 each, maximum
Russia (2010): 2,600
US (2009): 2,252
New Start: 700 each, maximum
Russia (2010): 566
US (2009): 798
Source: White House and Bulletin of the Atomic Scientists
It contains a full battery of verification measures to ensure compliance and it is equally important for the diplomatic signals that it sends in terms of relations between Moscow and Washington and for President Barack Obama's wider nuclear disarmament goals.
Managing the nuclear rivalry between Russia and the United States was a central concern of the Cold War years.
Tensions may have eased but reducing the size of each country's nuclear arsenals and ensuring that the new limits can be properly verified introduces a useful predictability in relations between Washington and Moscow.
The new Start follow-on agreement, as it is clumsily being referred to - perhaps the Prague Treaty might be a better name - reduces each country's arsenals to some 1,550 deployed nuclear warheads.
At present the US is thought to deploy some 2,200 warheads and the Russians somewhere between 2,600 and 2,700.
Under the new treaty each side will be allowed no more than 700 deployed ballistic missile launchers or heavy bombers equipped to deliver nuclear bombs.
How significant is this reduction?
US spokesmen claim that the new limit of some 1,550 warheads is about 30% lower than the target of 2,200 set by the 2002 Bush-era Strategic Offensive Reductions Treaty.
One heavy bomber counts as one nuclear warhead under the new treaty
And this was an agreement with none of the intrusive verification provisions of the new treaty.
However, some analysts wonder if the reductions will really be that significant due to the counting rules employed.
Each heavy bomber counts as one warhead irrespective of the fact that it might carry multiple bombs or missiles.
This means that in reality each side could well deploy more actual weapons than the 1,550 limit.
Numbers here are not hugely important though in the sense that these arsenals are still far in excess of what might be needed to deter each other or, for that matter, any other potential nuclear competitor.
This agreement really is a starting benchmark; a formal treaty that sets the scene for much more significant reductions in the future.
Indeed, much of the new agreement's importance is in its collateral benefits.
It marks an important improvement in US-Russia relations and it gives President Obama in particular an important boost ahead of next month's review conference for the Nuclear Non-Proliferation Treaty (NPT).
Bolstering this agreement, which is the central pillar of efforts to prevent the spread of nuclear weapons, is a high priority for Mr Obama.
Pressure on Iran?
He is hoping that this Prague treaty, and the recently announced shift in US nuclear strategy that restricts the circumstances under which nuclear weapons might be used, along with the forthcoming Washington Summit on securing nuclear materials will all prepare the way for successful review of the NPT.
There's hope too that better relations with Moscow will lead to Russia taking a tougher stance on Iran's nuclear programme.
Will better US-Russia relations put pressure on Iran?
Indeed, the US president's talks with his Russian counterpart in Prague are likely to focus on Iran.
However the significance of this new Start follow-on - or Prague Treaty - must be kept in perspective.
Almost a year ago in Prague, President Obama made a speech setting out his vision of a world without nuclear weapons.
Back in the Czech capital some 12 months on he is taking a very small step down that road.
Going further - even with the Russians - could take years of negotiation and still not bear fruit.
Iran and North Korea's nuclear ambitions have not been reined in.
And it is by no means clear that Mr Obama's arguments have yet won the day even in his own country, let alone among the other nuclear powers or countries like Israel, India and Pakistan who are thought to have significant arsenals of their own.