I discovered Salvation Army when I was 16, and I've been thrifting ever since. While I do buy some new clothes too, I've found that over the years, my favorite pieces are either vintage from my grandmother, or found in a secondhand store.
The thrill of the hunt makes thrifting fun (and like hunting anything, requires a bit of patience), but the ultimate rewards are finding and incredibly unique piece that you just won't get anywhere else. And it's so much more eco-friendly to reuse what already exists than participate in the resource-grab that making new stuff involves.
But if you've never done it before, thrifting can be daunting. Miles of clothes, sometimes disorganized, are presented in varying setups depending on the store. But if you have a plan, and some good advice (see below), you can come to enjoy this less commercial and more interesting way to shop. As with most things, practice makes perfect, so give yourself a few trips to the thrift store to figure out what works for you.
Wear comfortable, easily changeable clothes
Before you set out, be sure you're wearing something easy to change into and out of. You're definitely going to want to try the clothes on. I wear opaque black tights, a skirt and tank top with a jacket or shirt over it when I go thrifting, so I can try on pants or skirts easily (over the tights) and jackets and shirts (over the tank top), and often don't even wait until I get into a dressing room. This way I only bring to the change room (and sometimes there isn't one) the clothes I know already fit reasonably — and sometimes I don't need to use those changing rooms at all!
Do a once-over (i.e., get the lay of the land)
Spending your first five minutes walking around an unfamiliar store will immediately make you feel less overwhelmed. Check out where the men's, women's and children's clothes are, and where hats, accessories, shoes and other items may be. That will give you an idea of what you want to check out first. I always start with my favorite (and most coveted) section: women's dresses, since I will only think about what might be there while I look at other things. Then I move on in order of what I like to wear (so that way if I get tired or bored, I've covered the items I most love). For me, it's dresses, skirts, shirts, bags and belts, outerwear and lastly, pants (I don't wear pants much and find them uncomfortable).
Choose a rack and begin
Once you have chosen the section you want to start in (women's shirts, for instance), begin at the end of the rack on the outside edge and work methodically along the rack. Don't wander (that's what the initial once over was for), and if you are looking for specific items, I think flipping through each piece is actually the most efficient way to go. It sounds time-consuming, but at the end of the day, it's the most efficient process, and allows you to see everything; there are often hidden gems that you might not spot from the side of the rack and sometimes good stuff gets shoved inside a row of clothes.
Use your five senses
Look for stains (especially on underarms), rips and missing buttons; examine labels and look for good-quality brands that you're familiar with. That being said, I have a few pieces that were handmade/sewn and those don't have labels at all). Feel fabric for thin spots or low-quality materials (or scratchiness). If an item smells funny, put it back. Weird smells can permeate the rest of your wardrobe easily and are not worth the trouble they present, no matter how cool a piece is.
It's easy to buy too much when each item is so cheap. By being sure that you are really in love with a piece, you won't end up with a closet full of clothes that you don't wear. Even if you walk away with just one or two great items from an hour-long thrifting session, that's fine. It's quality that you should be concerned with, not quantity.