Are you really having this problem with activation, or are you having it after activation when you try to read a book?
If it is for a specific book ...
If it is a loan check it hasn't really expired.
Then verify that ADE and any devices are set to correct time and timezone.
If it is for registration ...
Sometimes ADE gets its registration/activation confused and in a semi-authorized state.
Uninstalling and reinstalling does not help.
Unfortunately, it often then gives misleading error messages about what is wrong.
A common incorrect message informs you that the ID is already in use on another computer and cannot be reused.
This can often be resolved by completely removing any authorization using ctrl-shift-D to the Library screen on ADE (cmd-shift-D if on Mac).
Restart ADE, and then reauthorize with your (old) Adobe ID.
In extreme cases on the mac, the following extra step has helped some people. Navigate to /Users//Library/Application Support/Adobe/Digital Editions and drag the activation.dat file to the trash. If you are using 10.7, see Access hidden user library files | Mac OS 10.7 Lion. http://forums.adobe.com/thread/1265248?tstart=0