It hurts the REPL experience a lot. You can still open the Console and execute JS in the context of your application, but you'll end up working in the transpiled JS, which might look very little or nothing like the source code you've been working on. It's annoying to the point that I don't bother doing it often any more. I think ClojureScript might be an exception to this, though, so if you're a lisper that's probably something you'd want to look at.