I've seen a few on here that have said they have been introduced to Nathan's work either here or by means of his time on Desperate Housewives and had never heard of Firefly before coming to this board. For those people I'm here to say, you owe it to yourself to visit your video rental place and pick up at least the motion picture Serenity, which is based on the series. Firefly was by far the best TV series nobody watched, cut down before it's prime by a network with an itchy trigger finger. And it's arguably Nathan's best work.
For newbies to the series, the easiest way to do things is to see Serenity first. It was made after the series as a means of wrapping up some of the major storylines left unresolved by the series' cancellation, but it was produced in such a way that you didn't have to be a Browncoat to understand what was going on. Joss Whedon included everything you need to know to understand the movie, even if you don't know every minute detail about the universe it's set in.
The movie has the advantage of being only an hour and a half investment of your time, vs. 14 hours for the series itself - it's a way to determine quickly if Firefly is for you (though I have yet to turn someone on to Firefly that wasn't a Browncoat by the end of it all). Hence why I recommend starting there.
However, the movie isn't as good as the series was. It does wrap things up nicely, but it suffers from the fact that there were nine major characters in the TV series, and in the movie, most of them (all of them, fan favorites for somebody) are just window dressing. Joss Whedon had to distill a season and a half of the series that would have been had the series survived down to an hour and a half, so something had to give - and as a result, there are times where the whole thing feels like 10 lbs shoved into a 5 lb bag. But it's still good viewing.
Required viewing for any fan of Nathan's work on Castle is the gag reels and blooper reels that appear with both the series and the movie. Nathan's character in the series, Capt. Mal Reynolds (aka Captain Tightpants), is so much more serious than Rick Castle is, the main way to see the jokester you've come to love on Castle is to see Nathan cutting up in the gag reels and blooper reels. You also get a peek at Nathan's bare ass.