CSmith wrote Physical disk defragmentation is almost never needed.

The server seems a lot slower than when I first set it up with DNN nearly two years ago.  I checked the disk defragmentation and there were red lines throughout the drive even after I defragmented.  It reported that it could not defragment the MDF file, so I assume that the red lines all over the drive represent parts of the MDF file.  I figure if the drive has to hunt all over to get parts of the database, perhaps that is at least partially a cause for the apparent performance drop. 

However, defraging Indexes is something that should be done to all databases. Using  DBCC SHOWCONTIG will show if you need to and the amount of fragmentation within the DB. There is a good MS post here that covers fragmentaion on SQL Server 2000 but also applies to 2005. Also note that SQL Profiler can be a power tool to indentify SQL performance issues. This along with the SQL Tuning Advisor may do the trick for you.

Excellent, I will look into both DBCC SHOWCONTIG and Profiler, and the tuning advisor.  Thanks for the tips!