The iPhone-Dev Team released new OSX versions of pwnage and quickpwn this morning for firmware 2.2.1 compatibility. For 3G users that want to upgrade to 2.2.1 and unlock you MUST use pwnage tool and disable the baseband update to conserve your 2.28.00 baseband. For first generation users there is no baseband update so just restore in iTunes to 2.2.1 and use the new version of Quickpwn to jailbreak.
A new version of Yellowsn0w has been uploaded for 2.2.1 compatibility as well so after you jailbreak add the source: apt9.yellowsn0w.com in Cydia and install version 0.9.7 and then reboot. This versions DOES NOT WORK WITH THE 2.2.1 BASEBAND so if you want to remain unlocked you MUST update with a custom firmware (via Pwnage Tool) that does not include the baseband update.