Syria envoy Kofi Annan has warned that if nations trying to end the country's violence fail to act they face an international crisis of "grave severity".
He says history "will judge us all harshly if we prove incapable of taking the right path today".
The talks hosted by the United Nations at its European headquarters in Geneva, Switzerland, are seen as a last-ditch attempt to salvage Mr Annan's peace plan.
Russia's determination to preserve its last remaining ally in the Middle East has collided head-on with US and other western powers' desire to replace Syrian president Bashar Assad with a democracy.
Diplomats are growing pessimistic that the UN-brokered conference can bridge the Russia-US divide.
Mr Annan added: "By being here today, you suggest intention to show leadership, but can you follow through?"