1. Know what you like - Sometimes I'll go in for something very specific. Last year, I wanted a teal suede blazer and found it! But more often I'm just looking for things that are in my wheelhouse: pink, cashmere, shiny, sparkly, beaded, vintage, or furry. So when I'm looking at sweaters, for example, I don't have to pull out every single one. Just the color or the shoulder is enough to see my favorite qualities.
2. Decide how tolerant you are of flaws - I don't mind a little wear and tear. It's tough to find a cashmere sweater with no holes at all. I once found a vintage coat with armpit tears where no one would see stitches, so I just patched with black felt. Personally, I like a little patina, especially if that means I'm getting something for 90% off, but if you want things to look new, you can still find some great stuff.
3. Learn to evaluate quality by feel - Before you go to the thrift store, walk through the expensive sections of a department store, and put your hands on the clothes. You'll get a sense of what high quality material feels like so you can pick out a gem out of the thrift racks by touch. You can also learn this at the thrift stores by keeping your eyes open for higher and lower quality brands and noticing how they differ in feel and construction. I did a lot of research to learn how to tell real Coach purses from fake, but one of the best things I did was go to the Coach store and just handle the real thing.
4. Decide how important quality and labels are to you - Some finds I get the most compliments on are not very high quality, but I'm easy on clothes, so they last a long time anyway. Also, because they can be trendy, they may not have been worn so much. I go with a high-low style of dressing and often wear a vintage Coach bag with a Target t-shirt. But that's just me. If you're a fan only of high quality clothes, you'll find some good options at also.
5. Decide whether you want to do the dressing room - If not, your best bets in clothing are sweaters, shirts and shoes. You can also have fun with books and jewelry. Or you can wear a form-fitting shirt so that you can pull things over it (I always forget to do this!) Some people wear leggings and try on skirts and pants right in the aisle. That's a personal preference. I don't own any leggings.
6. Decide how long you want to spend - If you don't have much time, target a couple of areas. I'm a sucker for cardigans and books. The departments are smaller, so it doesn't take too long to go through them.
7. If it's in your budget, spring for an item that pushes your style - Like a pair of tiger stripe, 6 inch heel, platform ankle boots. I don't wear them very much, but they are just right for the right occasion (like my birthday dinner.) Never would have paid full price for something I rarely wear, but part of the fun of thrifting is splurging on cool stuff and pushing your comfort zone. Even if you never wear it and end up donating it back, you've made a contribution to a good cause and learned a little bit about your own style.
8. Carefully check any items you're thinking of buying - This seems obvious, but if it's a coat or jacket, turn it inside out and check the lining and the pockets. I don't mind if a pocket is ripped, but if you do, you want to figure that out ahead of time. Also, remember that a faux leather purse or jacket will probably wear out more quickly than a real leather item. On the plus side, though, you can wear it in the rain since it's basically plastic. That's a useful quality.
9. Know how easy it will be to fix a flaw or make a change - Note that easier also means less expensive if you take it to a dry cleaner, tailor, or cobbler to have the work done.
Easy: re-sewing a button, darning a small hole in a sweater, hemming pants or skirts that don't have a lot of pleats, taking in a pants waistband or dress with side seams, anchoring loose beads, replacing the sole, heel, or footbed of shoes, stretching leather shoes a small amount, removing a fur collar, rewiring a lamp, tightening table or chair legs, getting out odors (internet search techniques for this).
Harder: fixing a zipper (potentially), taking in the seat of pants, patching hole in anything other than a sweater, especially in leather or fur, getting out stains (potentially), making any clothing larger (unless it has a very large hem that you can have dropped. Check before you buy.)
10. Remember that it's very hard to go wrong for $3.99 - If I hadn't bought that slinky, black, beaded, criss-cross-in-the-back, originally retailed for $500, wildly impractical evening gown that I thought I would never get a chance to wear, I could never have become a supermodel. (Okay, I'm not a supermodel. But I can't begin to explain to you how much fun I have had experimenting with being one. There is nothing for it but to try it yourself! Besides, you never know who else will want to wear your fabulous stuff.)