Although it has not been stated explicitly yet, there seems little doubt that Malaysia Airlines flight MH370 has crashed and probably with great loss of life.
Rescue will inevitably turn into recovery - of wreckage and bodies - and the search for clues will begin.
What happened aboard the Boeing B777-200 twinjet has already become the subject of much speculation, but it is important to recognise that answers will only emerge after a detailed investigation.
A team from the US National Transportation Safety Board (NTSB) will already be on its way to provide technical assistance to the Department of Civil Aviation of Malaysia (DCA), which will probably lead the investigation.
So what might they look for?
Weather can almost certainly be ruled out as a cause. Conditions have been described in different ways, but the consensus is that the aircraft was airborne in near-perfect flying conditions.
This leaves just two main possibilities - catastrophic mechanical failure or an act of terrorism.
Aircraft are complex machines, which require regular maintenance.
Investigators will undoubtedly examine the maintenance record of this aircraft to determine whether all the requisite checks were fully completed, on-schedule, and attempt to glean whether there were any recent unaddressed issues.
They will do so knowing that Malaysia Airlines has been battling financial uncertainty. The state airline has been losing ground to ferociously competitive low-cost carriers, which may have implications for aviation safety.
The airline is regarded as having a strong safety record, however. It last witnessed a major incident in 1995, after one of its aircraft crashed in the Malaysian city of Tawua.
The second and perhaps more frightening possibility is that an act of terrorism downed the airliner.
This incident comes just a week after 29 people were killed in a mass-stabbing in south-western China that authorities blamed on Uighur militants, and security has again been stepped up at transport hubs in China.
It is important to stress, though, that no-one has admitted carrying out an attack.
Until some clues appear, everything is just speculation and the loss of the airliner remains a mystery waiting to be unravelled.