Some iPhone users are reporting that their iPhones are unable to play music after upgrading to iOS 4.2.1. Fortunately, the fix is simple (for most). In fact, all you must do is re-sync your iPhone.
If you receive a message that the iPod app is unable to play your music after updating (you'll see a message that says something like, "There is no content on this device"), just connect it to your Mac and sync with iTunes as usual. Yes, that's it.
There seems to be additional trouble for those who are manually managing their music. One thread poster notes that he has to launch the iPod app, play a song and then sync every time new content is added, or the problem returns.
What has your experience been? Please share a fix if you've found it and help some folks out.