Assistive Devices must be on
Please check the following two things
It might be that iShowU has made a mistake (has a bug, gasp!). Click the Edit menu and check that the shortcut has been assigned correctly. The shortcut on the menu should match the one in preferences.

Here is an example showing the shortcut setup correctly in preferences, but not showing up in iShowU HD. This was from a previous build in HD that had a bug, but serves to illustrate what we're suggesting you check. This has been fixed in iShowU HD v2.1.1+.
