You'll need to contact the server in order to setup your Realm Works account and perform an initial sync of core material onto your computer. You'll also need to contact the server whenever you want to create a new realm, as well as when you want to get updates. Other than that, the server is currently not doing anything of note. So once you've created your account and created your realm(s), you can easily opt to work offline and not bother connecting to the server. The choice is yours.
I activated RW on my desktop PC, then activated the soft on my laptop to play away from home.
I couldn't play away from home, because RW wants to re-activate on my laptop each time I start the software (but I've got no internet connection when I'm not at home...).
I found a workaround, as I start RW at home on my laptop and re-activate it before going into sleep mode, but it would be nice not to have to re-activate RW each session...