Learning Python and the Mac OS X Cocoa Framework.

Cocoa with Python currently requires PyObjC, the Python-to-Objective-C bridge. See also this tutorial on how to write a Cocoa app in Python using PyObjC, including how to package the app for distribution to other Mac users. (They'll never know you wrote it in Python!)

PythonMac.org, links to resources for Python programming for Macs. Especially: the PythonMac.org wiki.

Oh, also: Ways to do OSA / AppleScript via Python.