This is truly brilliant anime, and one of my favourites. I won't summarise the plot as other reviews have covered that. One big aspect of this show which is mentioned above all else when Spice & Wolf is discussed, and which could serve to put you off watching, is the role which mercantile economics plays, which makes up most of the plot and admittedly quite a bit of dialogue. The main problem this presents is not the complexity it conveys - that actually serves to give the show depth, realism and immersiveness, even if (or perhaps especially if) it goes over your head as it did first time watching for me - but the fact that it does constitute a substantial amount of dialogue. It is by no means a large detraction (note still 5*), rather the only notable detraction. This anime stands out for its brilliant characters (even with only 2 real characters), especially the wolf spirit Holo, the lush and serene scenery rolling by, the banter between Holo and Lawrence and a refreshing and original plot based in medieval mercantile dealings rather than action (though I love action as well), predictability and plot convenience, as with so many anime.
It really is a beautiful show, intelligent, gently romantic, gripping and with a capability for the dramatic, this is probably the best anime I've seen.