I have read House of Leaves three times over the last ten years, and I'm still working on it.  Danielewski's book is an amazing puzzle, a truly outstanding work of fiction, and a haunting story about love, loss, and alienation.  

There are many nested levels of stories in House of Leaves, but at the most superficial level there are three: the Navidson family and the Navidson Record, Johnny Truant, and the Whalestoe Letters.  

Johnny Truant's story is the framing device.  (Well, one of them, anyway.)  Truant, a Los Angeles tattoo artist, junkie, and all-round punk, finds himself squatting in the apartment of a recently-deceased man named Zampano.  The contents of Zampano's apartment include a scholarly manuscript regarding "The Navidson Record."

The Navidson family, struggling and on the verge of divorce, moved to a large house in the country.  One day they discovered a closet that wasn't there before.  While investigating this strangeness they discovered that their house was half an inch larger on the inside than it was on the outside.  And things got really weird from there.

A hallway appeared in their living room, descending into the depths.  Will Navidson, his brother, and an assortment of friends, ventured into the maze together.  They filmed what became known as "The Navidson Record," which achieved international fame.  Zampano's manuscript about "The Navidson Record" includes commentary by all sorts of people whose names you would recognize (like Camille Paglia and Stephen King).  

(House of Leaves was published in early 2000, which means that it came after the release of "The Blair Witch Project" by only a few months.  The two works have nothing to do with each other, and yet there is a striking similarity between them.  Chalk it up to the universe's perverse sense of humor.)

As Johnny Truant reads Zampano's manuscript about the Navidson family, he (Truant) makes scribbled footnotes.  A diary of sorts, which creates a timeline of Johnny's life as he reads through the Navidson manuscript.  This forms an entirely separate storyline told entirely in footnote form, not unlike Nabokov's Pale Fire.

At the end of the book, the reader encounters a collection of mad poems and letters from Johnny Truant's mother, Pelafina.  Pelafina is committed at a psychiatric hospital, and her letters make about as much sense as you would expect.  

Except that Pelafina's letters are chock full of codes and secret messages which can be decoded by the clever reader.  (Or the reader who tries, gets frustrated, and ends up looking them up on the internet.)

The entirety of House of Leaves contains typographical oddities, like the way that the word "minotaur" is always printed in red, and the word "house" is always printed in blue.  Many more codes are embedded within the book, forming a network of secret communications between the various entities involved with the text.

At the most meta level, there is a clear connection between the Navidson's house and the book, House of Leaves.  The word "house" appears in a different color, the Navidson exploration finds a book called House of Leaves in the maze (but burns the pages for light, so it doesn't survive the expedition).  And what is a book, but a house made of leaves (of paper)?

If House of Leaves sounds confusing, it is.  But in a good way.  It rewards close reading, and re-reading, and is more than just an intellectual puzzle.  Danielewski builds suspense, poignancy, and fear into his narrative.  It is truly an amazing work of literature.