- It requires a running JVM to compile it all down (not a bad thing).

- Can take upwards of a second to compile depending on code base size and compression setting (even if the JVM is warm).

- Kills all ability to debug. Looks like "a.call().call()" etc.

That said, ClojureScript has been fun to work with, but IMO, Google Closure as dependency thwarts a lot of people looking to try it out like they might try CoffeeScript or TypeScript.