On June 24, 1982, a Boeing 747 operated by British Airways ran afoul of volcanic ash, resulting in the failure (for a relatively brief but probably eternal-feeling period) of all four engines. read more
The engines themselves can take tremendous abuse. The most credible causes of multiple engine failures on a Boeing 747 would be (1) bad fuel (which is why testing is so frequent and rigorous); (2) multiple simultaneous strikes by large birds on multiple engines; or (3) volcanic ash ingestion similar to that experienced by the BA 747. read more
Two engine aircraft are now routinely flying routes that when the 747 came out were illegal to fly with only two engines. It's a sobering thought to me when I board one that we're starting out with half the engines gone. At least it's still illegal for a two engine airplane to take off with one engine inoperative. I jest, of course. read more