ShedSkin is great if you don't want Python interoperability. Remember the excitement when they announced that Jython now runs Django? Cython allows you to run Django plus some optimized code, whereas there's currently no convenient way to make ShedSkin and CPython talk to each other. (And it's also the reason why hopes on PyPy are so high: A specializing JIT would allow you to combine all the flexibility and monkeypatching from CPython with the speed you normally only get from a compiler).
"Shed Skin is an experimental Python-to-C++ compiler designed to speed up the execution of computation-intensive Python programs. It converts programs written in a static subset of Python to C++. The C++ code can be compiled to executable code, which can be run either as a standalone program or as an extension module easily imported and used in a regular Python program."
Plus the maintainers is awesome, I was having suboptimal performance and he made adjustments within a few hours many times, making ShedSkin (and my program) much faster each time.