From the CiviCRM Upgrade for Drupal wiki article, step 9 indicates that all versions 4.0 or after require editing the civicrm.settings.php file, and provides two options to accomplish this.
CiviCRM 4.0 and above requires definitions in civicrm.settings.php which previous versions of CiviCRM did not have. There are two methods to put these required definitions into your install:
Create a "dummy" database and install CiviCRM fresh into that. You will need to rename or move your existing civicrm.settings.php. Running the installer anyhow will automatically create a correct civicrm.settings.php file. Then either replace that dummy database with your real one and proceed with the upgrade OR edit the new civicrm.settings.php to point to your real database. Add the definitions manually to your civicrm.settings.php file as below:
If your civicrm.settings.php does not have this section, copy and paste from here into civicrm.settings.php: [settings follow]
If the upgrade is starting from a version that is already 4.x, can we completely skip step 9 or what is the recommended way to handle this step?