Probably.
There are hundreds of top-level domains and thousands more second-level domains, but we've only personally registered domains under a few of them. Fortunately Wikipedia has lots of great documentation about each one.
If you're worried, do a little research: Lots of information is available if you search Google using queries like .io TLD, .tt top level domain, or register .es. If a particular registrar looks shady, look around for another one. If Domainr ever links you to a registrar that scams you—we haven't heard of this yet—be sure to let us know.
If you're still feeling uneasy, try to find examples of other people registering domains under whichever TLD you're checking into. A few good experiences by others can go a long way to helping you feel comfortable with some of the more exotic domain registration processes.
Update, 2009-02-20:
The Domains smartly recommends checking countries' laws, rules and regulations before registering country-code domains.
