On my current project, we use PowerShell scripts to automate our UI testing. We’ve been writing and running the scripts in the PowerGUI Script Editor, an excellent tool that’s also free. When we upgraded our application to run on version 4.0 of the .NET Framework from 3.5, we lost the ability to run PowerShell scripts in debug mode from PowerGUI.
The only work-around for this I’ve found (at least until a version of PowerGUI built on .NET 4.0 comes out), is a registry hack that forces all the .NET apps on the machine to use the latest version of the CLR. You can find more details in this user discussion at powergui.org, or this discussion on stackoverflow.com.