With openssl

• doc/smime-notes.txt
  
• MuttX509 is a walkthrough expanding on the original Equiraptor documentation which covers Mutt setup and configuration, as well as CACert integration.
  
• When exporting .p12 files from e.g. firefox, be sure to include all necessary intermediate CA certificates.

With GPGME

• First, you have to build mutt with --enable-gpgme
  
  • If your gpgme is 1.2 or newer, you have to patch the source before building. Otherwise you will see error creating gpgme context: Not operational
    
• Next, you should configure gpgsm:
  
  • Small HowTo on how to import freemail S/MIME certificates into GPGSM
    
  • Tutorial for gpgsm?
    
• ...and you set crypt_use_gpgme in your muttrc. (interactive :set crypt_use_gpgme doesn't take effect)