Of all the passages that Thomas Wolfe has written, his most famous is probably the concluding one that is also the title of his great Impressionistic novel. In You Can't Go Home Again, the main character, a writer named George Webber, has returned to his hometown of Libya, New York, only to discover that it has undergone a housing boom, and there is a superficial and frenetic atmosphere of change.  In a like manner, George's personal life has undergone a whirlwind of change as he has been involved with Esther Jacks, herself a superficial being.  After only so long, George turns from such a way of life, finding Esther's life in the circles of high society very artificial.  At the same time, Libya has been hit by the Great Depression, and the housing projects and their abandonment have wrought brooding loneliness, isolation, and desperation.  Oddly enough, Wolfe's hero reaffirms his religious beliefs and his faith in life.

After traveling through London, England, and then Germany where he has been on a train in which the Nazis detain a Jewish man, but the hero and the others must watch helplessly, George returns to write a lengthy letter to his editor in which he explains his beliefs and sets forth his artistic credo.  In Book 7 of the novel, George Webber explains that with the passage of time, old associations and friendships and loves cannot remain stagnant:

...And at the end of it [self-appraisal] he knew, and with the knowledge came the definite sense of new direction toward which he had long been groping, that the dark ancestral cave, the womb from which mankind emerged into the light, forever pulls one back--that you can't go home again.

... The phrase had many implications for him.  You can't go back to your family, back home to your childhood, back home to romantic love, back home to a young man's dreams of glory and of fame, back home to exile, to escape to Europe and some foreign land, back home to lyricism, to singing just for singing's sake, back home to aestheticism, to one's youthful idea of "the artist" and the all-sufficiency of "art" and "beauty," back home to the ivory tower, back home to places in the country, to the cottage in Bermuda, away from all the strife and conflict of the world, back home to the father you have lost, and have been looking for, back home to someone who can help you, save you, ease the burden for you,back home to the old forms and systems of things which once seemed everlasting but which are changing all the time--back home to the escapes of Time and Memory.

After George Webber returns from his travels through Germany, he realizes that no one can return to his hometown and have things seem the same.  For, the forces of time and change are too strong.