Sometimes it's a matter of figuring out "what have I just done?".
All of a sudden my URLs in emails stopped working. Outlook will say "cannot find the file specified", and Thunderbird just does nothing when clicked. I toggled default browser, and IE 8 would work fine, but Firefox 3.5 still no go. I found a report on Sophos scanning plug-in causing the issue. Of course I don't use it, but it did remind me that I just installed Flash Player 10 to check out a friend's new pictures from Tibet on photoshop.com. That action added an extension (content download manager) as well as a plug-in (Flash 10.0.32.18)
So I removed the extension. No help. Then I disabled the plug-in. URLs came back to life! Then I re-enabled the plug-in, and things stayed OK.
Something not very smooth between Flash 10 and FF 3.5.2 then. As usual, they need to do a better job testing. Granted I'm an advanced user with unique needs sometimes, but look at this long thread with annoyed users and webmasters alike, you know they could definitely do better...