Each character is one of the Garou, the werewolves of legend. The Garou are neither a true species (by our standards) nor a hybrid of man and wolf: the child of Garou and wolf or Garou and human may be Garou (10% of the time); the child of Garou and Garou is a metis, a malformed mule. Additionally, Garou have something of a two-tiered caste system: There are thirteen tribes, related by blood, and five auspices. A character's auspice is determined by the phase of the moon under which he is born: the full-moons, Ahrouns, are warriors; the gibbous-moons, the Galliards are the bards and storytellers; the half-moons, the Philodoxes (philodoxen?) are the judges; the crescent-moons, the Theurges are the mystics; and the no-moons, the Ragabashes, are the tricksters.
Characters group together in packs, like wolves, which is a useful tool for keeping PC groups together; they may not all like each other, but they are like unto a family.
The Garou exist to protect the Earth (Gaia) from the depredations of the all-destructive Wyrm, once a peaceful spirit of destruction and path-clearing turned insane. And the Wyrm is everywhere. Environmental pollution is of the Wyrm. Overpopulation is of the Wyrm. Drug abuse, suicide, child abuse, war, starvation, poverty: all these things are manifestations of the Wyrm. Many Garou see the culling of mankind's population as the only real way to defeat the Wyrm, while others feel that this would only be succumbing to its wishes.
The Wyrm's all-encompassing nature makes "him" both a useful creation and a pain for gamemasters. The Garou fight the Wyrm, and nearly anything can be seen as a manifestation of the Wyrm, and can thus be used as a target for Garou activity. On the other hand, it is sometimes annoying to have nearly every activity the PCs go through, every wicked plot, be traceable to this being. Admittedly, the Wyrm is so insane as to barely be sentient, and really only acts through hundreds of minions, most of whom do not get along, but he is still there, behind everything.
The sourcebook Rage Across New York is excellent; it portrays a villain the Garou can't beat with claw and tooth alone, or even with a great deal of legwork, brilliant strategies and magic. The villain is child abuse, and the cycle of abuse it engenders. This is clearly the Wyrm's work on earth, but it does not have to have an evil spirit behind it to make it a frightening, intricate foe that the characters take seriously.
There are a couple of other good sourcebooks for Werewolf, but unfortunately, lots and lots of Werewolf product is crap. The majority of the Tribe Books that have been published so far are poorly-written, though most of them have a handful of good ideas and perspectives in them. They seem to be pandering to a younger crowd, and to the "White Wolf Groupies", the people who will buy any WW product just because it's got that cool little paw on it.
I was a wizard on GarouMUSH since its inception over two years ago; I have a lot of experience with Werewolf's theme. We spent a lot of time on Garou fleshing out what day-to-day Garou life must be like, details that aren't really needed in a face to face game. I will say that it took me two and a half years of daily play on GarouMUSH to begin to tire of the theme, and we didn't cover everything that could have been done. There's a lot to do with the game, if you are feeling creative.