As I write (at 9:40pm EST in the US, 0240 March 8 GMT), things look bad for Malaysian Airlines flight 370 from Kuala Lumpur to Beijing, but nothing is known for sure.
The most illuminating information I have seen so far is this log from Flight Aware. It shows that the airplane had leveled off at 35,000 feet -- and then suddenly was not transmitting any more information about its location, speed, altitude, or rate of climb or descent.
[Update: Flight Aware is imperfect, as I've written here many times. Also, the Lat/Long of its last report for this flight is over the Malay peninsula and is less than one hour after takeoff, versus the 2 hours that we've heard in many news reports. This goes into the category of "All early reports about air incidents are contradictory, confusing, and often wrong." But still the indications are not good.]
It is hard to imagine a systemwide failure of the transponder and other reporting equipment that could have made the plane stop transmitting any information and yet still be flying along safely. And in that case, it would presumably have tried to land somewhere along the Malay peninsula or in Indochina.
The main insight I have to add for now is: Whatever happened, it is unlikely to reflect chronic shoddiness with Malaysian Airlines, which in my experience is a good, competent, and modern airline (I have flown MAS many times, including during the two years I lived in Malaysia in the 1980s, and more recently along this route), nor with the Boeing 777, a good and well-experienced airplane. Beyond that, we await further news with best wishes for all involved.
12-hours-later update: Flightradar24 has more detailed reporting on what appear to be the plane's last known positions, over the South China Sea.