The series' protagonist is an asthmatic 12-year-old boy, Arthur Penhaligon. The series begins on a Monday, with the main events starting a week later on the next Monday. Each book moves onto the next day of this week, concluding on Sunday. Each day features beings, collectively known as the Trustees, who each govern a portion of the House, which is the centre of all Universes. The seven demesnes of the House are, in the following order: the Lower House, the Far Reaches, the Border Sea, the Great Maze, the Middle House, the Upper House, and the Incomparable Gardens.
In the beginning of the first book, Arthur lives a relatively normal life as an adopted child in a large and caring family. An asthma attack on a Monday that should have killed him brings him to the Lower House, where he is to find the cure to a plague brought to his world by its agents. By convenience, he is declared Heir to the Kingdom, and given the Lesser Half of the First Key, which is shaped like the minuteclock. Because of this Key's magical properties, Arthur is relieved of his asthma, and proceeds to a strange and dangerous set of adventures.
As Arthur discovers, the Will of the Architect (Creator of the House and the "Secondary Realms" that surround it) was not fulfilled as it should have been. Instead, it was broken into seven pieces by the Architect's Trustees, the Morrow Days. The Will was forced to act on its own, and its First Part chooses Arthur to be the Heir to the Kingdom. It thus becomes Arthur's responsibility to recover each of the missing pieces of the Will, defeat each Trustee - each of whom has been afflicted with one of the seven deadly sins - and claim their domain by taking their respective Key, and discovering the hidden secrets of the house.
The Keys to the Kingdom are seven objects of power given to the Trustees along with command over their demesnes. It is unknown whether, but implied that, control of the Key is that which gives one control over a demesne and its namesake day in the Secondary Realms. The Key will bond to the rightful owner of a Key, and protect him or her from harm, though not from discomfort. A rightful owner of a Key is an Heir, the Trustee to whom it was originally entrusted, or a Steward. Over time, the use of a Key will irreparably turn a mortal into a Denizen, though it is mentioned that after a few centuries, this process may reverse a little.
The Keys hold sovereign power in their own demesne and their day. All other Keys are of equal power when they are not in their realm. The exception to this is Sunday's Key, which is paramount over the others. They can do much of what is asked of them, such as opening, locking, manipulating, and freezing items. The full powers of the Keys are not known, as of Lady Friday. According to Arthur, the Keys have the ability to kill anything they wish, be it Denizen, mortal, or Nithling. Beings that are none of these, such as the Architect, her consort the Old One, and their three sons and indeed possibly Arthur in later books may be immune.
Nothing is the mythical substance used in the series. From it the entire Universe formed through a concentration-based process. It appears as oily black smoke, or a black liquid, and contains the properties of being able to dissolve (with the exception of immaterial objects) or create anything. When enough Nothing comes together, it can form a Nithling. Nithlings are creatures not created by the Architect, but self-made from uncontained or uncontrolled Nothing. The Nithlings have this autonomy in common with both the Architect and the Old One, but apparently lack the power and creative impulses demonstrated by those elder beings.
Nithlings are animal-like entities formed from Nothing. They are feared by most of the House due to their ability to kill even an immortal Denizen with a festering bite. Nithlings take a variety of shapes and are incorporated into every book in some form. They appear to lack complex intelligence, although some types can be used as servants (notably the Fetchers, sent to retrieve the Key in Book One). Most lower forms of Nithling can be dispatched with silver or salt, though this has little effect on higher or more substantially Made Nithlings.
Nithlings dissolve into Nothing when killed. They are employed by many Denizens and the Morrow Days for menial tasks, especially when someone is needed to venture into the Secondary Realms. Nithling species usually are named; this implies that they are usually made in regular forms. The Nithlings seen so far in the books are: