My main problem with it is that it can add a lot of extra syntax which -- while immensely useful for static checking -- is never executed in production. PEP 484 includes support for stub .pyi files, which contain the typing, but IDEs still don't take advantage of that.

pytype is nasty when you're trying to set a return type for a function that was previously returning different types (e.g. let's say different protos).