You can see the supported databases here 

http://world.episerver.com/documentation/Items/System-Requirements/EPiServer-CMS/Version-6/System-Requirements---EPiServer-CMS-6-R2/

Never tried to install it on RDS. Probably worth doing a proof of concept PoC on before promising anything. Getting Episerver 7 to run on Azure wasn't a piece of cake. 

Might work, might be a world of pain...

I've run epi 7 on AWS using RDS. RDS has support for SQL Server 2008R2 so you should be able to run epi 6 as well.

Be aware that some features aren't available using RDS, for example backup/restore using management studio and FILESTREAM support (if you're storing your blobs in db).

Use a case insensitive collation btw. I know that one got me when I tried running on some weird SQL server once. Some SPs in Episerver had some issues with casing... :)

Thanks for all the responses, some great information here. 

To sum up, it sounds like it's possible but not officially supported. 

Also - anyone know if using RDS would require a EpiServer cloud license (which aren't avialbe for 6)? I'm assuming not since this is a SQL replacement rather than affecting the number of the instances. The actual web server would still be a VM tied to an IP/MAC license.

License, scheduled jobs, search and cache invalidation for load balanced servers are a few others I would expect can cause some head aches if you want a cloud based Episerver 6 solution.  

Well, using RDS only means that your db is hosted in the cloud. It does not mean that you'll need a cloud license. RDS is not as you stated a SQL replacement, rather SQL Server in a container managed by Amazon.

Also, if you decide to host your application in an EC2 with a reserved IP you could still use the old license type. Even if you would like to scale it out on several EC2 instances you could still use the old license type if you have reserved IP addresses on the instances. 

The reason to use the cloud license type is mainly because with auto-scaling you might not have a static IP or MAC to bound the license to.

The areas you mention I believe would cause headaches if you decide to run your application in a container like Beanstalk or Docker. If you run EC2 instances and utilizing auto-scaling that is. For an EC2 setup where you control the instances manually, using static IP's and so on would give you the same possibilites as other hosting infrastructures, with the ability to utilize windows services, configure remote events and so on. You'll lose the main purpose of using the cloud though :)

Yup. I agree. Just worth mentioning that since Epi 6 i depending on windows services for some functionality and UDP broadcasting for events you might run into some troubles there if you treat it as any random .NET website. Version 7.5 and up is much more cloud friendly btw :) 

Thanks again for the insights, this is all really helpful.