Book of Cain refers to the character Deckard Cain, whom Diablo fans will remember as both a companion and quest giver though the first two games. Cain acted as the player's touchstone for the lore and history surrounding both the player's adventure, as well as the world of Sanctuary.
Though a constant source of information, Cain's remarks were usually veiled in secrecy. He told you what you needed to know, always hinting at something much bigger happening the background. Unfortunately, the fragmented information also left holes and inconsistencies within the grander Diablo storyline. Book of Cain is designed as an "in-game" tome of information detailing every bit of lore players have wanted to know, all from Cain's point of view.
Without going into extreme detail (I'll leave that surprise for readers), Book of Cain is presented as a journal of the history of Sanctuary from someone who watched it happen. The journal is written for Cain's adopted daughter, Leah, who will play a major role in Diablo III's story and serves as a guide for not only what has happened, but has yet to come.
The first section details the story of The Dawn, and the creation of the eternal conflict. From there, Cain offers a detailed look at the creatures of hell, including Diablo and Baal, as well as lesser demons, like Belial and Andariel. Cain also offers up profiles of heaven's denizens, such as Tyrael. Each section is accompanied by amazing illustrations of each. If you've ever spent time with a Blizzard instruction book, you already have an idea of how amazing the artwork looks. With Book of Cain, you get even more of it.
With the story of creation out of the way, Cain then moves into the events that took place during Diablo and Diablo II. Here the book gets even more interesting for fans, offering a concise story of what happened and how those events will flow into Diablo III. Any inconsistencies between lore versions are dealt with using notes scribbled in the margins. The deeper you get into the book, the more you'll find yourself turning the book to its side to decipher Cain's markings. It's a neat concept and works well with the book's overall presentation. The notes also drop hints as to who certain characters are (including Leah), and offer bits of information that will (I assume) be brought to light in Diablo III.
As an added bonus, Book of Cain also includes a detailed map of Sanctuary, which is folded up and stored in an envelope attached to the back part of the book. It's a neat addition, and is even suitable for framing if you're a fan looking for something different to hang on your wall.
Diablo III: Book of Cain is as close to Diablo's story bible as players will ever get, and an enjoyable read for long-time fans.