The Manual of Witchcraft and Alchemy is an evil spell-book given to Winifred Sanderson by the Devil himself; written in blood and bound in human skin, it contains the recipes for her most powerful and evil spells.
The book's cover is made mostly from pieces of human skin stitched together, is adorned with snake-shaped ornaments, and has a lock which can keep the cover shut. Its pages are written in human blood. It also has a human eye on the front cover which is often closed in sleep, and only wakes to the calls of its endlessly doting mistress. This means that the book is actually sentient and highly intelligent.
As an unholy record of evil magic bestowed by the Devil himself, the book itself is protected by magic, and therefore cannot be burned or destroyed by traditional means.
Among its contents is the life potion, an evil potion that allows the sisters to suck the life-force of the drinker to replenish their youth. Other spells include cursing a victim with immortality, transforming victims into cats, raising the dead, cursing victims with boils and blisters, and numerous others.
Its most important curse was that if in the event the sisters were killed, that should a virgin light the Black Flame Candle on Halloween during a full moon, the witches would return alive for one night unless they suck the life out of a child lest they turn to dust come sunrise.
Despite the fact that it was created to solely serve nefarious purposes, and that nothing good was supposed to come from it, its contents still detailed a confirmed weakness of the Sanderson sisters (which could be used against them): a circle of salt could protect their intended victim from their powers.
After the sisters' deaths, it was last seen in the witches' cottage, opening its eye, and presumably remained there. While Jay and Ernie are still trapped in their cages, the eye on the book's cover opens, indicating the book is still alive and all-powerful, and indicating a chance the Sanderson sisters could return somehow.