Ever get this while debugging a Web project in Visual Studio?
I get it all the time. It happens when I move projects around and forget to give the ASP and IIS user permission to the folder. If you run w/out the debugger, you'll get the following more obvious error message.
System.Web.HttpException: Server cannot access application directory '...'. The directory does not exist or is not accessible because of security settings.
Goto Folder Properties | Security and give access to the ASP.NET Machine Account and the Internet Guest Account. Next you may or may not incur a similar dialog but w/ a new error message; The project is not configured to be debugged. The happens when you're missing a Web.config file or when the Web.config file does not allow debugging.
I hit this problem so frequently, I figured it was worth more documentation so that next time I'm programming under the influence of alcohol, I'll more easily find my way home ;)