This is based on the F. Scott Fitzgerald short story that begins:

As long ago as 1860 it was the proper thing to be born at home. At present, so I am told, the high gods of medicine have decreed that the first cries of the young shall be uttered upon the anaesthetic air of a hospital, preferably a fashionable one. So young Mr. and Mrs. Roger Button were fifty years ahead of style when they decided, one day in
the summer of 1860, that their first baby should be born in a
hospital. Whether this anachronism had any bearing upon the astonishing history I am about to set down will never be known.

I shall tell you what occurred, and let you judge for yourself.

Brad Pitt will play Benjamin Button, who is born as a feeble old man, and ages in reverse until he becomes a baby at the end of his life. Fitzgerald noted that "This story was inspired by a remark of Mark Twain’s to the effect that it was a pity that the best part of life came at the beginning and the worst part at the end."

Button is from a well-to-do family in Baltimore, Maryland. He is able to live a relatively normal middle portion of his life when his biological and chronological ages are not too drastically far apart, but has more problems at either end. The story is in part comic and part melancholy.