The main reason not to use PyPy is that Perl 6 is a gradually typed language, that is some type information is available at compile time. And that makes PyPy a

The main reason not to use PyPy is that Perl 6 is a gradually typed language, that is some type information is available at compile time. And that makes PyPy a less-than-ideal target platform. (It actually seems that runtime environments that are optimized for statically typed languages, but have some support for dynamic stuff, suit Perl 6 better than dynamic runtimes. The CLR and JVM backends have the best run time performance so far, but they suffer from large startup times, which is something that the Perl community is very sensitive to).