Well, out of the 5 deadly space program accidents involving crews, 3 of them have been re-entry accidents. Two were Russian, and the Columbia makes it the third.

Time's science correspondent had this to say about potential causes:

TIME.com: What are the possible scenarios that could have caused this disastrous accident on the shuttle's reentry into the Earth's atmosphere?

Jeffrey Kluger: There are three possible scenarios that explain this event. The first, which I believe is the likeliest explanation, would be an aerodynamic structural breakup of the shuttle caused by it rolling at the wrong angle. Remember, after reentry, the shuttle is descending without power, which means astronauts at the controls can't compensate for a loss of attitude by using the engines, they can only do so using the flaps. And that's extremely hard. Astronauts describe piloting the shuttle on reentry as like trying to fly a brick with wings. It's very difficult to operate, and even more so to correct any problems.

A second explanation might be a loss of tiles leading to a burn-through. (The shuttle is covered with heat-resistant tiles to protect the craft and those inside it from burning up in the scorching temperatures caused by the friction of reentry.) But I think that explanation is unlikely, because the tile-loss would have had to have been quite substantial for that to become possible. You'll hear a lot in the next few days about things falling off the shuttle during liftoff. But it often happens that they lose a few tiles, and I'd be surprised if it happened on a scale that could make an accident of this type possible.

The last option is some kind of engine failure leading to fuel ignition. Although the main tanks are mostly empty, there should still be fuel left in the maneuvering tanks. But probably not enough for an explosion that could have caused this breakup.

And just in case anybody was wondering, you can almost certainly rule out terrorism as a cause. This incident occurred well above the range of shoulder-fired missiles. And it would probably be easier to sneak a bomb onto Air Force One than to get one onto the shuttle.