Sometimes you run into that frustrating fish that just doesn't want to cooperate. They may be visible and even visibly eating but they just don't want what you've got. Before the expletives here are a few things to try:
Go lighter on your tippet - Many fish that see a lot of presentations simply learn what to look for and will begin to avoid tippet. Try lighter tippets or even flourocarbon tippets in a size or two sizes smaller than the norm. Of course you may pay once you hook up if it's too light but at least you'll get to that point.
Try different presentations - Don't be afraid to adjust the angle of your presentation, the side of the fish your drift is on, or the depth. Sometimes you have the right fly but just not the right presentation. Try to get your fly over the fish without putting your line over the fish, or try a deeper or more shallow drift with a nymph, try a twitch, or sometimes with streamers and nymphs I'll sink the fly right to the bottom just in front of the fish and they will pick it up as it sits.
Try different flies - Of course this is the easy answer that everyone comes up with but think a little creatively here, it can pay off. Sometimes rising fish aren't eating adult insects so try a humpback emerger, RS2, or other similar emerger pattern under the surface. Also, don't be afraid to try something crazy. A Chernobyl Ant or hopper pattern when fish seem to be eating tricos or other small bugs can surprise you. A streamer pulled in front of rising fish may trigger a strike too. And of course there is always the tried and true method of finding just the right pattern by making small adjustment to try to match the local insects. I really like to go with thin sparse patterns whenever I get refusing fish.
I had the chance to fish for 15 minutes yesterday and found such a snotty fish. After a few dries, a few nymphs, and a several consistent refusals I laid a krystal bugger on the bottom just in front of him. After it sat for a few seconds I gave it a quick twitch and let it fall back down. The fish, a nice rainbow, rushed up and sucked it in right off the bottom. It was a great reward for some persistence.