The UN envoy to Syria, Staffan de Mistura, has described fresh peace talks in Geneva as a "moment of truth".
But neither Syria's government nor the opposition appear ready to compromise over the future of President Assad.
Diplomats are hoping to build on a fragile and partial truce which came into effect at the end of February.
The talks come as government forces reportedly launch an assault on so-called Islamic State's (IS) positions near the world heritage site Palmyra.
IS and the al-Qaeda-linked Nusra Front are not included in the current cessation of hostilities.
Syrian warplanes and helicopters as well as ground troops were involved in the assault on Palmyra, according to the UK-based Syrian activist group, the Syrian Observatory for Human Rights.
Also on Monday, there were reports of demonstrations against the Nusra Front in territory it holds in Idlib province in north-western Syria.
Photos and videos circulated on social media by an analyst with the Brookings Institution think-tank showed supporters of Western-backed rebels marching in the town of Marat al-Numan.
There were also reports the protestors had stormed a Nusra Front prison, freeing detainees.
That followed attacks by the Nusra Front on Free Syrian Army (FSA) bases in Idlib reported over the weekend.
'Mother of all issues'
The UN-led talks represent the first serious diplomatic intervention since Russia began air strikes in September.
Speaking before the negotiations, Mr de Mistura said "the mother of all issues" was political transition and the only alternative was a return to war.
But on Saturday Syrian Foreign Minister Walid Muallem ruled out any discussion on the future of President Assad.
US Secretary of State John Kerry responded by accusing Damascus of "trying to disrupt the process".
The main Syrian opposition umbrella group, the High Negotiations Committee (HNC), said the pre-conditions could halt the talks before they had even started.
On Sunday the HNC said it would push for an interim government in which President Assad and the current leadership would have no role.
Mr de Mistura has said he wants presidential elections to be held in the next 18 months.
The two sides are not meeting face to face, and Mr de Mistura is starting the negotiations with a meeting with the government delegation.
A cessation of hostilities agreed by most participants in the conflict began late last month - but there have been reports of some violations on all sides.
Syrian rebels have rejected Russian allegations that they used missiles to shoot down a government warplane, saying it was downed by anti-aircraft fire.
The rebels said the reports may have been aimed at accusing some countries of supplying the opposition with anti-aircraft missiles.
More than 250,000 Syrians have been killed and about 11 million people have been forced from their homes during the civil war, which began with an uprising against Mr Assad five years ago this week.
Government forces, supported by Russian air strikes, have made gains against rebel fighters in recent months.
Media downbeat on Geneva talks - BBC Monitoring
Syria's government-owned al-Thawrah daily says the talks "will bring nothing new".
The ruling party's al-Ba'th paper accuses the opposition of trying to impose its agenda "regardless of what Syrians want".
Writing on the website of the Syrian opposition Orient News TV, Basil al-Awdat accuses Staffan de Mistura of having "no clear plan for the talks... but the Syrian opposition should go to Geneva and give him a last chance".
The Saudi-owned, London-based al-Sharq al-Awsat says the UN is "simply performing a facelift on the regime... the talks are destined to fail even before they begin".
Iran's main TV1 channel highlights Syria's UN representative, Bashar Jaafari, complaining that Damascus does not know "who we are negotiating with and what the issues are".
Russian Channel One TV stands out from the crowd by maintaining there are "high hopes".