After the 1991 Gulf war, US officials hoped the Iraqi leader would be overthrown by internal opponents from within the army.
When that failed to happen, US policymakers watched in frustration as a range of UN-backed policies from economic blockade to aerial bombardment failed to dent the power or defiance of the Iraqi leader.
Now the US argues that Saddam is developing an arsenal of weapons of mass destruction that could threaten the stability of the region.
The relative ease with which the US effected a change of regime in Afghanistan appears to have convinced the administration that it can achieve a similar outcome in Iraq, in alliance with internal and external opponents of the regime.
These include semi-autonomous Iraqi Kurdish groups in the north, Shia Muslim groups in the south, whose leadership is based in Tehran; several senior army officers who have defected; and Ahmed Chalabi's Iraqi National Congress, which claims to act as an umbrella for numerous other exiled opposition groups.
Kurdish groups do not want to back the US aims until they know who is going to follow him
Mustafa Alani, a strategic analyst at the Royal United Services Institute in London, believes the US has stated its objective so clearly that there is no going back, but sees comparisons with the Afghanistan operation as "totally wrong".
It has been suggested that Kurdish groups in northern Iraq could play a key role in any US military action to unseat Saddam Hussein, mirroring the role of the Afghan Northern Alliance in toppling the Taleban.
But relying on the Kurds would be politically difficult for the US because this would be opposed by the US's key ally, Turkey, says Dr Alani.
Turkey, which borders Kurdistan and Iraq, is host to US and British planes patrolling the skies over Iraq and its role could be crucial in a military engagement.
Ankara would oppose a role for the Kurds for fear that they would seize the opportunity to establish an independent Kurdish state - setting a precedent for Turkey's estimated 12 million Kurds.
Kurdish leaders are in any case reluctant to jeopardise the gains they have made by throwing their weight behind military action against Saddam Hussein.
The leaders of both main Kurdish parties, the Kurdistan Democratic Party (KDP) and the Patriotic Union of Kurdistan (PUK), have said that they will not help to topple Saddam Hussein unless they know who the next president will be.
Massoud Barzani, head of the KDP, said: "We are not custom-made revolutionaries... We will never become an orderly in the hands of the US or any other force."
US wary of Shia
In southern Iraq, the Tehran-based Supreme Command of the Islamic Revolution in Iraq (Sciri ) commands the loyalty of most of Iraq's Shia community, which represents over 60% of the population.
The Iraqi army could be the key to a new era
But they were badly let down during the failed rebellion of 1991 when US promises of support failed to materialise.
Moreover, the risk of the emergence of a regime dominated by Shia Muslims linked to Iran is clearly a deterrent for the US.
Leith Kubba, an Iraqi analyst at Washington-based think-tank the National Endowment for Democracy believes the Bush administration is distancing itself from tribal leaders, the Kurds and the Shia Muslims.
"They are the most relevant on the ground but their political agenda is so problematic in the long term that they are not being taken on board," he said.
Encouraging military revolt
Dr Kubba believes the Iraqi army will be the most important partner on the ground for the US.
It is uncertain, however, how the army will respond to US calls to revolt, given the fact that many military officers have a stake in the regime's continuation.
Iraqis have been plagued by war and shortages
Dr Alani does not exclude a ground offensive by US troops, but sees this as very much a last resort.
It would be politically difficult for Kuwait to allow itself to be used for anything other than back-up forces, and out of the question for Saudi Arabia to allow its territory to be used for a ground offensive.
Dr Alani believes that the US is coming round to the view that its best option in the case of Iraq is to create instability and encourage a military revolt inside Iraq - perhaps with the assistance of some US special forces as in the case of Afghanistan.
What follows Saddam?
Some analysts suggest that US ground forces, operating from Turkey, could be used to move into the vacuum after Saddam's removal to prevent the "wrong" people from seizing power.
But there is no obvious candidate capable of uniting Iraqis under a new government.
Washington has recently courted several former Iraqi army officers. Of these, General Naguib Salihi is the least tainted by association with the Iraqi regime.
The author of several studies on the Iraqi army, including a book on the failed uprising of 1991, he left Iraq in 1995 and came to prominence when he revealed that he had been sent a videotape showing the rape of a female relative by intelligence personnel.
His refusal to be intimidated, publicly denouncing the brutal tactics of the regime, has won him admirers.
However, he does not appear to have ambitions for political leadership and has argued that the military should not be directly engaged in politics.
The most prominent of the civilian opposition leaders is Ahmed Chalabi of the Iraqi National Congress (INC) - one of a number of Iraqi opposition figures who relocated from London to Washington when the US administration began funding them during the Clinton presidency.
He has proved an effective lobbyist in Washington, but Dr Kubba sees the INC as a spent force.
"It tries to sell itself to the Iraqi people on the strength of US support, but it really has no support inside Iraq any more. The leftists and former communists and Islamic groups inside the country who once allied themselves with the INC have now distanced themselves from it."
Dr Alani is also doubtful of the effectiveness of the exiled opposition. "They have no base or popularity in the country and have proved this by their inability to organise anything, even a demonstration, inside Iraq during the past 11 years," he said.
Dr Kubba hopes that the US will not overlook the two million or so Iraqis he estimates are living in exile and who have so far been reluctant to speak out.
They will have a crucial role to play in persuading people inside Iraq that there are grounds for hope and in rebuilding the country's political institutions and legitimising a future government, said Dr Kubba.
He believes that although people inside the country remain paralysed by fear, there is no evidence to suggest that Saddam Hussein's regime has any popular support at home and every reason to believe that ordinary Iraqis would welcome a new regime with huge relief.