There are some fairly obvious ways to set up a chess board that cannot possibly happen: both kings simultaneously in check would be one.
There are some positions that seem impossible in a normal game... for example, one side has all of it's original pawns in their original location and the other side has NONE of its pawns remaining - but with both sides displaying all pieces in their original positions (perhaps knights can do this, I don't know.)
However, seems like there may be some impossible positions that are not at all obviously difficult.
The question is if there are any known legal positions (preferably ones that a normal human might think are the result of a game) that cannot be played into?