L'Aquila was where nearly 300 people were killed in a quake in April, and an evacuation plan is in place in case a tremor should hit during the summit.
Security is also high, and at least 36 protesters have already been arrested.
The leaders' agenda includes the global financial crisis, food security, climate change and Iran.
US President Barack Obama will attend the summit along with Russian President Dmitry Medvedev. The two men have just agreed a framework for new nuclear weapons cuts in Moscow.
The leaders of Britain, Germany, Italy, France, Canada and Japan will also attend, along with EU representatives.
But Hu Jintao, China's president, has cancelled plans to attend the summit and address G8 leaders, instead flying back to Beijing amid continuing unrest in China's western province of Xinjiang.
Tremors predicted
The summit is being held at the same police barracks from where the rescue operation was run after April's earthquake, when more than 50,000 people were forced to flee their homes.
The region has continued to suffer aftershocks, including one of magnitude 4.1 just last week.
A top geologist predicted there would be more tremors this week - but said the summit venue should be safe.
Nevertheless, an evacuation plan is in place. Italian newspapers say it involves moving the leaders to tents and then flying them out by helicopter.
Italian Prime Minister Silvio Berlusconi moved the summit to L'Aquila to show solidarity with the quake victims. He will take Mr Obama on a tour of the town on Wednesday.
He may also be hoping to use the summit to put his domestic troubles behind him. His wife has filed for divorce and he has faced myriad accusations about wild parties and relations with young women and prostitutes.
Officials will be hoping for more positive headlines than when Italy hosted the G8 in Genoa in 2001. That summit was marred by violent protests and police faced charges of brutality and misconduct.
But on Tuesday, police in Rome said they had arrested 36 people after masked protesters blocked roads, threw objects and set fire to tyres.
Big agenda
The first item on the agenda on Wednesday will be the global financial crisis. The credit crunch was not even envisaged at last year's summit, when concerns were considerably different - high oil and food prices and inflationary pressures.
Now discussion will centre on how to avoid a repeat of the credit crunch, with regulation to force banks to hold higher capital reserves a favoured option.
There will also be pressure to conclude new talks on global trade rules, and to avoid protectionist measures.
International political issues like the Iranian election aftermath, the Middle East, nuclear weapons and terrorism will also feature in discussions.
And the leaders will try to get closer to a new deal on climate change management ahead of a crucial meeting in Copenhagen in December.
African leaders will join the three-day summit on Friday, to push for a new initiative to fund farming in the developing world and tackle global hunger.
