The ruling gave legal legitimacy to a practice Israeli forces have routinely used against members of the Palestinian factions during the past six years.
The Israeli human rights organisation B'tselem estimated that 339 Palestinians were killed in the targeted operations over the past six years.
Of those, 210 were the targets and the rest were bystanders.
While Israel has largely put the controversial operations on hold as part of a Gaza Strip truce declared last month, defence officials say they are still the best last resort for preventing attacks by faction members who cannot be easily caught and prosecuted.
"Israelis with their might and the support of the US administration can afford not to be moderate and to dictate their terms"
Be Humble, UK
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The high court, rejecting petitions filed by a pro-Palestinian lobby and another rights group in 2002, ruled that the state's arguments could have legal merit in some cases.
The three-justice panel said: "Arrest, investigation, and trial are not means that can always be used. At times, no such possibility exists; at times it involves such a great risk to the lives of [Israeli] troops, that it is not required."
Palestinians cried foul at the ruling.
"Assassination is a form of crime that cannot be justified," said Saeb Erekat, an adviser to moderate Palestinian president, Mahmoud Abbas, who shares power with Hamas, sworn to Israel's destruction. "It is unbecoming of a nation state."
A senior Israeli jurist said the ruling will help military commanders facing war crimes lawsuits.
Shai Nitzan, deputy state attorney, told Israel's army radio: "A ruling of this kind provides enormous protection."
A pro-Palestinian group tried to have Moshe Yaalon, the former chief of Israel's armed forces, arrested as he visited New Zealand last month, but was blocked by local legal authorities.
According to an Israeli newspaper, the group wanted Yaalon tried for ordering a 2002 air strike on a Gaza apartment block that killed a Hamas chief along with at least 14 civilians.
In its ruling, the high court laid out parameters for what it deemed acceptable "collateral damage" in such circumstances.
"Attacks should be carried out only if the expected harm to innocent civilians is not disproportional to the military advantage to be achieved by the attack," it said.
"For example, shooting at a terrorist sniper shooting at soldiers or civilians from his porch is permitted, even if an innocent passer-by might be harmed ... However, that is not the case if the building is bombed from the air and scores of its residents and passers-by are harmed.
"Between these two extremes are the hard cases. Thus, a meticulous examination of every case is required."