How to use Drupal in the cloud with on demand instances Services such as Rightscale do lots of things to help mange unpredictable traffic and bring more servers online when traffic spikes. 

Is it possible to use Drupal with services such as this?

While Drupal can be set up for a number of configurations, is it possible to set it up so the configuration is flexible. 

What do you need to do to make sure it works?

Assuming that you can bring on demand instances online, what do you need to do to make sure that Drupal will work in this situation. What do you have to do?

What is the optimal setup?

Once you have done what you have to do, what should you do to ensure that you can scale to more servers seamlessly. What is the best configuration in terms of number of servers. How many caching servers should you bring on line for each web server. Should you scale each tier independently?

edit

Edit to clarify that this is to do with the implications of on demand scaling for a Drupal site.
Rackspace put together a pretty decent start to this subject here which uses a couple of specific technologies which you might not want to use, but the principles are the same.

You might also need to look at Mysql clustering, but only really if you're hitting serious traffic levels