This article covers an interesting topic that has shown itself in my current project: using the Cache across appdomains and web farms.

In the end his solution is basically to create a mechanism to write out cache information to files that each app domain watches for changes (or so I gleamed from glancing over it) but in our case we are storing little bits and pieces and not large things. In other words, the added overhead of reading/writing to the filesystem would probably eliminate the benefit of using the cache for our application.