In a lengthy interview with NPR published Sunday, Defense Secretary Leon Panetta addressed the drone campaign against al-Qaeda that he oversaw as head of the Central Intelligence Agency, explaining that when a target was identified, a shot would not be taken if it meant women and children would be at risk.

"Frankly, we made very clear that if there were any women or children that were involved that we would not take a shot. That became a rule that we abided by," Panetta told NPR.

But such strikes have not come without hundreds of civilian casualties, according to a New America Foundation estimate. And a 2010 Washington Post story by Peter Finn and Joby Warrick detailed Panetta's decision to sign off on the effort kill al-Qaeda-allied Taliban commander Baitullah Mehsud, which also resulted in the death of Mehsud's wife:

On the morning of Aug. 5, CIA Director Leon Panetta was informed that Baitullah Mehsud was about to reach his father-in-law's home. Mehsud would be in the open, minimizing the risk that civilians would be injured or killed. Panetta authorized the strike, according to a senior intelligence official who described the sequence of events.
Some hours later, officials at CIA headquarters in Langley identified Mehsud on a feed from the Predator's camera. He was seen resting on the roof of the house, hooked up to a drip to palliate a kidney problem. He was not alone.
Panetta was pulled out of a White House meeting and told that Mehsud's wife was also on the rooftop, giving her husband a massage. Mehsud, implicated in suicide bombings and the assassination of former Pakistani prime minister Benazir Bhutto, was a major target. Panetta told his officers to take the shot. Mehsud and his wife were killed.

A U.S. official told NPR a strike with non-combatants in the area would only happen in "exceptional circumstances against very high-level terrorists." Panetta defended the agency's overall tactics, saying: "My mission, whether it's at CIA or here, is to keep the country safe. And I thought the ability to use these kinds of tools and operations to go after those who would attack our country -- I felt that they were legitimate if we follow the law."

In an interview with NBC News' "Meet The Press" Press Pass published Sunday, Panetta said the process of establishing targets was an "intricate" one:

"You know, as a Catholic, I remember when I first became director of the C.I.A., and realized that I was making life-and-death decisions -- with regards to our operations. It doesn't come lightly. You've gotta be -- you've gotta really think about it. You gotta make sure that we really are focused on somebody who is, you know, who is a direct threat to the United States -- someone who intends to attack the United States and hurt -- hurt our people. And you've gotta be able to go through the process. And it was an intricate process, not only of establishing the targets, but going through the legal requirements to ensure that we were doing this carefully. And then, also, then the operational side to make sure that we -- we limited the, the collateral damage.

Panetta also told NBC News he believes there should be more transparency and oversight with regard to the drone program, something human rights activists have advocated.