Anything that directly interfaces with the system can cause problems. I generally run into trouble with sort on EBCDIC platforms, though file paths are another source of trouble. VMS files are just odd (especially with revisions).

I usually write my files and find someone who can test them on other platforms. If you sign up for a Compaq Testdrive account, you can run tests on several different platforms. They've been really good to Perl QA.