The Varnish HTTP Accelerator Integration module integrates Drupal with Varnish, a reverse proxy which sits in front of Apache, PHP and Drupal. Varnish stores cached content in RAM and avoids the overhead of Apache and the Drupal bootstrap. As such it offers very high performance for anonymous users on cached pages and is the preferred option for many sites where scaling is paramount.
Varnish requires either a patch to core to add HTTP headers, PressFlow or Drupal 7. Most people are therefore running Varnish in conjunction with PressFlow.