Newer versions of .Net and .Net core has have removed and/or changed “Code Access Security” (CAS) since this question was asked.
We used CAS for our Applications was not really to hard, since we'd only tried to stop unauthuorized code execution. Problems came up once using our software from local network share, but a cas-policy cleaned the problem out.
Since update of .NET3.5 our problems were not existent anymore, since code on local area network is now handled like local code.