About 5% of the email addresses in your list will become obsolete each month. Part of your mailing campaign is collecting bounced messages and placing them in a database. Try to re-mail to these bounce-backs. Sometimes the email addresses are good but didn't reach the recipients because of network problems or outages. If the messages still bounce back after the re-mail, remove the addresses from your mailing list.
Prevention is always better than reaction, so remember to give the folks in your database an easy way to notify you if their contact info changes. The account maintenance page on your web site should allow users to change email addresses, update personal profiles, and perform other housekeeping items that help keep your organization's email marketing database up to date.