If you create a CiviCRM group with, say, 1,000 contacts in it and then go to create a mailing using the same group and it only says it will send it to 750, it's likely because some of those contacts are "on hold." On hold simply means that the system has determined the email address associated with the contact to be not worth sending to (i.e., dead). This could be caused by the emails bouncing for any number of reasons.

To avoid unnecessary continued bouncing, CiviCRM flags them as On Hold and prevents them from being included on future mailings.

So far there isn't much you can do automatically to take care of these emails. Your only option at this point is to generate a report of these contacts and either delete them or perhaps call each user and see if you can get an updated email address from them.

An overview of generating this report can be found on the CiviCRM wiki.