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Copy of a message by Christian Heimes on a duplicate report:
 
For effective SSL server cert validation a bundle of trustworthy CA certs is required. Most system ship such a bundle but it's not always possible to access the bundle from Python / OpenSSL. Windows and Mac OS X come into my mind. wget and curl ship a copy of Mozilla's CA cert bundle.
The site http://curl.haxx.se/docs/caextract.html explains how to extract the CA certs in PEM format. I suggest that we ship the CA bundle with Python and use a lookup chain:
- user defined path to a cacert directory or cacert.pem file
- cacert directory or PEM file in the user's home directory: 
 cacertdir = os.path.join(site.USER_SITE, os.pardir, "cacert")
 cacertfile = os.path.join(site.USER_SITE, os.pardir, "cacert.pem")
- system's ca cert directory (/etc/ssl/certs on Linux)
- CA cert bundle shipped with the Python installation.