A statement of hopeless despair, analagous to "shit happens". In the world of Atlas Shrugged it is asked by those who are afraid of looking for causes of their problems, preferring to hide behind a cliche.
Immediately before he went on strike the man John Galt was working as a researcher at the Twentieth Century Motor Company. The old owner of the factory, John Starnes, had been a stern man who demanded nothing less than the best from his employees. Once he died, it was taken over by his three children; Ivy, Eric and Gerald. They held a general meeting and announced that the company would be run on a new policy: From each according to his ability, to each according to his need. In essence, the factory was now a worker's collective. John Galt stood up and walked out of the plant, saying that he would stop the motor of the world.
When the factory went under, the few workers who remained travelled across the country as vagrants. When they saw the American economy begin to plunge and society begin to unravel, they saw that the young researcher had made good on his threat. They began to try and find him, to talk him out of it, to win him back along with the philosophy he championed, to no avail. They cried out "Who is John Galt?" and others, not understanding the reference but all too familiar with the sentiment, took up the cry.