<p>I am just beginning to do research into the feasibility of using Amazon's SimpleDB service as the datastore for RoR application I am planning to build. We will be using EC2 for the web server, and had planned to also use EC2 for the MySQL servers. But now the question is, why not use SimpleDB?</p>

<p>The application will (if successful) need to be very scalable in terms of # of users supported, will need to maintain a simple and efficient code base, and will need to be reliable.</p>

<p>I'm curious as to what the SO communities thoughts are on this.</p>

Well, considering simple DB doesn't use SQL, or even have tables, means that it's a completely different beast than MySQL and other SQL-based things (
http://aws.amazon.com/simpledb/
). There are no constraints, triggers, or joins. Good luck.
Here's one way of getting it up and running:
http://developer.amazonwebservices.com/connect/entry.jspa?externalID=1242
(via
http://rubyforge.org/projects/aws-sdb/
)
I suppose if you're never going to need to query the data outside of rails, then SimpleDB may prove to be OK. But as it's not a first-class supported DB, you're likely to run into bugs that are difficult to fix. I wouldn't want to run a production rails app in a semi-beta backend.