"They must be comfortable," people say. Surprisingly, I usually respond, "not really." That's not their purpose I say. "At least, not a first," I correct myself. "You basically have to wear these every day for 6-8 weeks straight before you get used to them." Wearing fully-insulated, arch-supporting, padded, comfortable shoes spoils your feet and make your muscles lazy. These take you out of that comfort zone and put you nearly on-par with how humans were created to walk and run: barefoot.
Of course, going about in barefeet isn't exactly safe, so what's better than awesome Vibram soles to protect you? And that's the entire point. Aren't those barefoot running Kenyans who seems to always win the big name marathons? How can that be? Well, perhaps they're running the way we were meant to (except for the paved asphalt road).
Given my recent back & health [hypertension] problems, a caveman diet (meat every now and then [when the hunt is successful] then veggie at other times), and trying hard at reducing the amount of garbage I send to landfills (consume less, generate less garbage, etc.), trying to significantly reduce my impact on this planet, getting these shoes was a logical step and nearly a no-brainer. What should you know before getting yours?
One: they're not normal. Well, you already knew that, but sizing them for your feet will confirm that. You don't order by "shoe size." You order based on the length of your longest foot. Use this calculator: http://www.vibramfivefingers.com/size_fi
Two: there are many counterfeits online. All the "real" color combinations can be found on Vibram's website. Anything else more exotic is likely a knockoff, which are bad in most ways from what I understand. Be sure to order from an authorized retailer with a brick-n-mortar storefront.
Three: once you get 'em, you need to be able to put 'em on. Do it in the same way as you'd put on a glove for your hands: get your fingers (toes) all the way in, then slip the back on, tie the strap, etc. It'll take time (days, weeks) to get used to them. You'll discover you want to land more on the ball of your feet rather than the heel... not a problem. You will take shorter strides, also good. In general, you're gonna land on the front half of your foot more than the back half.
Four: my goodness, I don't think that my feet stink, but this is ridiculous. The good news is that you can just toss them into the wash. I also carry a travel size can of Lysol with me. The real secret best practice for me: hairdryer on full/hot as soon as you take them off... don't give time for bacteria to significantly form/grow. The hairdryer dries the moisture and fries the germs. If not, then the dosage of disinfectant after they're dry will take care of that. You'll know when this is less effective and that you should throw them in with your laundry. When you take them out, use a cloth to dry out any initial water followed by your normal routine with the hairdryer and disinfectant spray.
Five: not so great on a rainy day or wet sidewalks. The FiveFingers Flow is better when there's a lot of water or if you wish to swim with them, but the Classics and KSOs just get all wet, squishy, and icky inside! If you have to wear them for hours like I did in Jakarta with tropical rainstorms throughout the day, they were just nasty by the time I took them off on my hotel room at night! The Flow is also better in cold weather from what I've read. I know this because from a hot & humid 95F/35C Indonesia, I went to a chilly 36F/2C Berlin right after.
Anyway, YMMV. Good luck and enjoy!!
Here I am to the left, with the FiveFingers KSO ("keep stuff out") shoes in the San Francisco Giants orange and black colors to the left while my EuroPython 2011 colleagues show off their FiveFingers Classic shoes. You can see the KSOs are aptly named as there is an additional layer to resist sand, pebbles, and other road/trail debris from getting inside. (photo taken in Firenze, Italia [Florence, Italy] courtesy of Ade Oshineye)
Below are links with more info about "VFFs" as they're commonly called, other best practices, stories, and general information about barefoot walking/running: