This series is, in short, about a mysterious medicine seller who travels around in order to seek out and destroy Mononoke, a type of unnatural spirit that exists in the human world. They can only be destroyed using a special type of sword, but that sword can only be drawn under certain circumstances. The series is divided up into several arcs, each of which deal with a different mystery and Mononoke.
Mononoke is a spin-off of the Bakeneko arc from the anthology series Ayakashi. I'd recommend you watch that before Mononoke if you're interested, but really, you could watch it without seeing Ayakashi first and still understand what's going on just fine.
