To open Outlook in safe mode, first close Outlook if it is currently running. Then, press and hold the "Ctrl" key while clicking on the Outlook icon to open it. This will prompt a message asking if you want to start Outlook in safe mode. Click "Yes" to continue. Safe mode is useful for troubleshooting and identifying issues with Outlook add-ins or extensions, as it disables them temporarily. Once you have finished using Outlook in safe mode, close the program and reopen it normally.