The main issue will come with any C-coded extensions you may be using: depending on your system, but especially on Windows, such extensions, compiled for 2.5, are likely to not work at all (or at least not quietly and reliably) with 2.6. That's not particularly different from, e.g., migrating from 2.4 to 2.5 in the past.
The simplest solution (IMHO) is to get the sources for any such extensions and reinstall them. On most platforms, and for most extensions, python setup.py install
(possibly with a sudo
or logged in as administrator, depending on your installation) will work -- you may need to download and install proper "developer" packages, again depending on what system exactly you're using and what you have already installed (for example, on Mac OS X you need to install XCode -- or at least the gcc subset thereof, but it's simplest to install it all -- which in turn requires you to sign up for free at Apple Developer Connection and download the large XCode package).
I'm not sure how hassle-free this approach is on Windows at this time -- i.e., whether you can use free-as-in-beer compilers such as mingw or Microsoft's "express" edition of VS, or have to shell out $$ to MS to get the right compiler. However, most developers of third party extensions do go out on their way to supply ready Windows binaries, exactly because having the users recompile is (or at least used to be) a hassle on Windows, and 2.6 is already widely supported by third-party extension maintainers (since after all it IS just about a simple recompile for them, too;-), so you may be in luck and find all the precompiled binaries you need already available for the extensions you use.