I’ve just found and installed the following add-on for Mozilla Thunderbird:
It allows you to use a different S/MIME certificate for each of the different identities (i.e. “e-mail address aliases” or “profile aliases”) you defined in your Thunderbird profile.
It’s currently still marked as an experimental add-on and I’ve noticed a minor glitch in v0.3.0 when using it (see my add-on review), but this might also be related to the fact that I also use the Virtual Identity add-on (another nice add-on which allows you to use an arbitrary sender address for sending messages).
The “S/MIME Security for Multiple Identities” add-on is very convenient if you have multiple e-mail accounts and want to use S/MIME message signing and/or encryption with all of them.
Bonus hint: You can get your own, personal S/MIME certificates for free at Thawte (for e-Mail only) or StartCom/StartSSL (also offers free class 1 SSL/TLS certificates for FTP servers, web servers etc. -> the latter don’t “work” with Internet Explorer, however).