There are two reasons that I can think of that I have experienced. First, IPython simply doesn't behave like standard Python; you can have very obscure corner-case bugs in otherwise-normal code because of its magic. Second, if you're using PyPy, you don't get to use IPython.

Edit: I meant that PyPy isn't compatible with most of the things people use IPython for, like Numpy and Scipy, not that IPython's shell doesn't work on PyPy. Sorry.