Thunderbird uses themes to customize its user interface. You can download themes from the Internet and write your own themes.
There is limited support for customizing the Thunderbird toolbars. Without using extensions, only a small set of predefined buttons can be added to the toolbar. Extensions can add more buttons to the group you can select from.
As with any program, it is important to back up Thunderbird's profile. The profile contains the configuration for the user and that user's email. Lose the profile and you also lose your email.
Extensions create new functionality in Thunderbird. They are easy to install, and you can write your own extensions.
By using the about:config extension, many of Thunderbird's preferences can be altered to suit your needs. The extension frees you from the problems of trying to manually edit prefs.js and user.js.