Why would a kill -2 not work?

[Peter Steele]

Under what circumstances might a "kill -2 nnn" not work. I have a Python app with a signal handler configured to catch INT signals. It seems to work fine, but we've recently noticed that after the app has run for a while the kill -2 no longer works. This seems pretty suspicious, perhaps indicating our app is misbehaving in some way. What might cause the signal handler to stop working? 

Is there a better list for this question?