But critics cite human rights abuses against non-combatants and question the legality of targeted assassination. Others wonder if drones presage a time when robotic weapons play a role in making lethal decisions.
Last week the New York Times reported the White House had sought "to develop explicit rules for the targeted killing of terrorists by unmanned drones".
But the push to codify when strikes are legitimate has divided military planners, who want more operational freedom, and officials who advocate caution.
Attorney General Eric Holder cites the "imminent threat" threshold. "We are at war with a stateless enemy, prone to shifting operations from country to country," he said in March. President Barack Obama admits that exactly when and how unmanned weapons can be used "is going to be a challenge for me and my successors for some time to come".
That challenge involves balancing security with human rights.
A recent study, "Living Under Drones," by the New York University School of Law and Stanford University's International Human Rights and Conflict Resolution Clinic, says drone strikes exact a terrible civilian toll.
It cites more than 130 interviews with victims, witnesses and experts, plus figures compiled by the Bureau of Investigation Journalism.
The study reports "mass trauma" among civilians, caused by UAVs that loiter over targets.
What makes a legitimate UAV target? The US "kill list" distinguishes between "personality strikes" on known individuals, such as al Qaeda's Anwar al-Awlaki, killed in Yemen last year, and "signature strikes" against groups.
It is strikes against the second category that draws most criticism, with disagreement on whether this target represents "middle management" - bomb makers, document forgers, arms procurers and such - or ordinary foot soldiers.
The NYU/Stanford study asks if anyone "who might be described as a 'militant' can be lawfully intentionally killed" by UAVs unless "directly participating in hostilities with the US or posing an imminent threat".
"If it's lawful, ethical and moral to use force, then it's lawful, ethical and moral to use drones," says Ben Wittes, a senior fellow and research director in public law at the Brookings Institute.
Concerns have also been raised about "blow back": tribal people who become radicalised by drone strikes, and seek revenge, their anger exploited by jihadists.
"The problem with the drone is it's like your lawn mower," an ex-CIA analyst told the Washington Post. "You've got to mow the lawn all the time. The minute you stop mowing, the grass is going to grow back."
Victims are pushing back against this contentious policy. In a closely watched case at the high court in London lawyers acting for Noor Khan, a Pakistani whose father was killed by a drone, question the legality of strikes.
"The participation of a UK intelligence official in US drone strikes, by passing intelligence, may amount to the offence of encouraging or assisting murder," Martin Chamberlain, acting for Khan, told the court in October. "Alternatively, it could amount to a war crime or a crime against humanity."
Two court cases in Pakistan argue US drone strikes on Pakistani territory are acts of war, a hot issue given widespread opposition to attacks.
In addition, the UN has appointed two rapporteurs to examine drone strikes and other extrajudicial killings that have allegedly killed civilians.
Speaking to students at Harvard Law School, Ben Emmerson, one of the rapporteurs, said alleged follow-up drone strikes used against rescuers, and other attacks on funeral mourners would, if true, constitute war crimes.
The US neither confirms nor denies its drone policy, but senior officials justify the strikes, said Emmerson. "In reality, as I think the administration must be aware, it is holding its finger in the dam of public accountability."
350 Strikes using drones in Pakistan between 2004 and 2012 have killed between 2586 and 3375 people, including about 472 to 885 civilians, of whom 176 were children. Between 362 and 1052 people have been killed in Yemen, with 58 to 170 fatalities in Somalia.
3 Strikes alone in Pakistan left 50 civilians dead Deadly force.