After nearly a year of tough negotiations, the signing by Barack Obama and Dmitry Medvedev in Prague, the capital of a former Soviet satellite now in NATO, will symbolize cooperation between Washington and Moscow for the sake of global security.
Both presidents say new cuts in the largest arsenals on the planet are a step toward a world without nuclear weapons and a signal to nations seeking them that there is no need.
But the successor to the 1991 Strategic Arms Reduction Treaty (START I) will not come into force without ratification by lawmakers in both countries, and could face a rough ride in the US Senate.
Analysts say it will be no cure-all for Russian-American relations, which have improved after hitting a post-Soviet low during Russia's 2008 war with Georgia but remain troubled by a range of disputes.
The START successor deal will not resolve simmering tension over missile defense, which has haunted ties since the Reagan era and hurt them badly in the past decade.
With Russia already saying it could withdraw from the pact if its security is threatened by US missile defenses, the divisive issue could come to the fore again.
Russia has long complained that cutting its offensive arsenal could leave it exposed if the United States builds a missile shield in Eastern Europe. Prime Minister Vladimir Putin clouded hopes for the offensive weapons pact by suggesting in December that it should also limit missile defenses.
The pact is expected to acknowledge a link between offensive and defensive weapons, but US officials have stressed it will not restrict the development of missile defenses.
The United States says its defensive plans are no threat to Russia. But Moscow's concerns about missile defense and Western conventional weapons superiority mean further nuclear arms cuts Obama hopes can follow will be far harder to secure.
"It took 10 months, but this treaty is going to be fairly easy compared to the next one," said Steven Pifer, a senior fellow at the Brookings Institution.
Negotiators missed an initial target of Dec. 5, when START I expired, and failure still seemed possible until both sides announced late last month (March 26) that Obama and Medvedev would meet in Prague on April 8 to sign the pact.
The treaty would limit the number of operationally deployed nuclear warheads to 1,550 for each country - down nearly two-thirds from START I and 30 percent lower than the ceiling of the 2002 Moscow Treaty set for each side by 2012.
The signing will be the first major concrete foreign policy achievement for Obama, who has sought to "reset" Russia ties.
