h,
I believe it is time for the list; you may very well need 4) or 6); 5) is hardly relevant.
The following is a general list of things you may try when the issue is not in a specific file, and when it is not caused by issues with opening a file from external media, see below. You may have tried/done some of them already; 1) and 2) are the easy ones for temporary strangenesses, and 3) and 4) are specifically aimed at possibly corrupt preferences); 5) is a list in itself, and 6) is the last resort.
If possible/applicable, you should save current artwork first, of course.
1) Close down Illy and open again;
2) Restart the computer (you may do that up to at least 5 times);
3) Close down Illy and press Ctrl+Alt+Shift/Cmd+Option+Shift during startup (easy but irreversible);
4) Move the folder (follow the link with that name) with Illy closed (more tedious but also more thorough and reversible);
5) Look through and try out the relevant among the Other options (follow the link with that name, Item 7) is a list of usual suspects among other applications that may disturb and confuse Illy, Item 15) applies to CC, CS6, and maybe CS5);
Even more seriously, you may:
6) Uninstall (ticking the box to delete the preferences), run the Cleaner Tool (if you have CS3/CS4/CS5/CS6/CC), and reinstall.