First, you will need to create a Do Not Mail query if you don't already have one.  This query will pull all of the accounts you will want to remove from your mailing.

Second, you need to create a compound query to subtract the Do Not Mail accounts from your standard query.  In the steps below we will use the standard LYBUNT query as an example:
  1. Click the Queries button on the menu bar
  2. Select a category that you want to store this query in (Ex: Base)
  3. Click New Compound Query under the tasks menu
  4. Name the query LYBUNT Mailing List
  5. Set the Data Return Type to Accounts
  6. Select the Subtract icon under Combine the Queries
  7. Set Query 1 to  LYBUNT & SYBUNT: LYBUNT - A
  8. Set Query 2 to  the category you stored the query in: Do Not Mail - A
  9. Click Save And - Preview