Set the hook as soon as you see anything out of the ordinary. Sometimes it is only a tiny slow down during a float/swing of the indicator. When fishing calm water, you might only see a rotation of the indicator rather than the indicator being submerged. The faster you set the hook the better. As the length of the leader increases, so must the aggressiveness of the strike. Hit 'em quick, hit 'em hard.
The biggest reason for missing those quick, tiny hits are because they are often from small fish slashing at your fly. Bigger fish are more deliberate and usually your indicator goes down nicely.