I'm probably a bad person to talk to since I have 3 bikes that I ride, and they were all custom frames. The first was really the important one, since the others ended up based on that one. I went to a custom frame builder - Peter Mooney - who has a one-man custom bike operation and is also co-founder of what I consider to be the best bike shop in the Boston area (Belmont Wheelworks). Peter measured me, and watched me ride on a trainer. We talked about what I was planning to use the bike for - in my case, loaded touring. Our first meeting was all about the frame. Later on, I returned to the shop and we talked about and chose components. I have to say that the custom bike experience was one of the best times I had spending money! At the time I bought this bike, there didn't appear to be many good touring bikes out there, and I wanted a bike that fit me well and a bike that I could rely on. Rather than compromise on the frame I decided to go totally custom. My other 2 custom bikes are Bike Fridays, and I was able to use the measurements from my Peter Mooney bike as a starting point.
One of my co-workers just had a custom Independent Fabrication bike made. His is a much more high-end road bike where mine was made for touring. He's had his bike less than a month, and so far is very happy with it. He also went to Belmont Wheelworks and had a fit done - then they ordered the frame, and later built the bike with the components that he chose.
Custom frames come at many different price points, so I'd recommend figuring out what your price range is ahead of time. If your LBS doesn't normally deal with the type of fitting and custom bike building that you're looking for - is there another LBS close to you that does? Or do you live in a low-bike-shop area?
Have fun!
--- Denise