Today I encountered an interesting issue with Server 2008 and the email router. The email router is running on the same server as CRM, and I had just configured CRM to run in IFD mode. This somehow broke the email router. When browsing the CRM URL from the server, I received the IFD login page. Thinking I had missed a subnet, I confirmed that all appropriate subnets (including the server subnet) were included in the IFD tool, and verified it was working by testing from another server. Everything checked out.
And yet somehow, the request for CRM was coming from another IP not included in the subnet, but only when browsing from the CRM server itself. It turns out that the CRM server, when making the request to itself, was making that request using IPv6 instead of IPv4. The IP address was indeed different and was not in one of the included subnets. To resolve this issue, I disabled IPv6 on the ethernet connection (in the properties, I simply unchecked the IPv6 box) and tested again. Everything worked fine, and the router was fixed.
So if you are using an IFD, keep in mind that Server 2008 may try to make requests in IPv6 to itself, and the CRM server will think these are external requests.