I use a heavily modified version of Case Tracker, a group of addon modules for the Drupal CMS. It's similar to other helpdesks (it's actually a fork of the project and project release modules that are used at drupal.org) and it's being extended by a student during this year's Google Summer of Code.

Since Case Tracker runs in Drupal it's just one feature of an entire suite. I have all the features I need, from web-to-email, email-to-web (posting by email or phone), XML-RPC, a full range of access controls, wiki functionality, RSS feeds, etc.