Responsible for a volatile theater of operations that extends from Kenya to Kazakhstan, the high profile general must also keep an eye on extremism in Pakistan and Iranian influence in the region, all under the orders of a new US president.
Sent to Iraq in 2007 to salvage the explosive situation there, Petraeus is credited with turning around a Sunni insurgency in the west and using a 30,000 troop "surge" to secure Baghdad and its environs.
Many hope that Petraeus will bring his counter-insurgency expertise to bear in Afghanistan as he did in Iraq, where levels of violence have dropped sharply and combat deaths are now at the lowest point since 2003.
The intensifying violence in Afghanistan has put the "forgotten war" on the front burner and has pushed the White House, the Joint Staff and Petraeus to launched strategic reviews of what the general has called the "longest campaign of the long war."
The reviews extend to the extremism in Pakistan and the sanctuaries in its northwestern tribal areas from which the Taliban and Al-Qaeda launch attacks into neighboring Afghanistan.
As it waits for these reports, Washington has already committed to send reinforcements to Afghanistan as US force levels decline in Iraq, to bolster the 70,000 NATO and US troops there.
Both presidential candidates, Democrat Barack Obama and Republican John McCain, advocate sending more troops to Afghanistan, which they promise to make a priority.
At the same time, calls have been made from a variety of sources in favor of a dialogue with the Taliban insurgents, following the Iraq model.
Petraeus, who emphasizes the importance of political and economic efforts in defeating an insurgency, has publicly said the United States should "talk to enemies," as has Defense Secretary Robert Gates and Afghan President Hamid Karzai.
"There is talk, not surprisingly, of a 'surge' for Afghanistan, and hope that we can soon accomplish there what has begun to take root in Iraq," wrote Michael O'Hanlon, of the Brookings Institution, and Andrew Shearer of the Lowy Institute.
But they warn that conditions are different in Afghanistan. There are fewer troops, the country is poorer and has less resources, and the insurgent sanctuaries in Pakistan are destabilizing.
Relying on local tribal militias also is risky in a country that historically has been ruled by warlords beyond the control of the central government, some experts say.
Added to the long list of challenges that await General Petreaus is Iran, which the United States accuses of seeking to develop nuclear weapons and of trying to keep the pot boiling in Iraq by supporting insurgents.
"In Iran, we face a tremendous threat to regional security, and also the country most likely to test the next US president," said Jon Alterman of the Center for Strategic and International Studies.
