So, the next time you go to select a different fly, tie on a smaller tippet instead and present the same fly again. You'll be surprised at how often the fish will take the very fly they've been refusing. What may have happened if you're using a commercial tapered leader, is that you've cut off most of the tippet from constantly changing flies and you're now tying your fly to a leader that is much too thick. Just tie on a one to two foot section of the next smaller diameter or pound-test and you're back in business. If you're constructing your own leaders, just continue tapering down another diameter or pound-test before attaching your fly.
This tip won't always work, of course. You may already be fishing with the tiniest possible tippet, or the fish may be refusing because they really are taking something completely different than what you're using. But, just put the suggestion in your memory bank and give it a try the next time you're going fishless.