After two brief scenes that at first seem unrelated to the rest of the film, we see a dark-haired, obviously rich beauty in the back of a limousine. Her driver stops at an odd location on Mulholland Drive, which is a twisting, thickly wooded two-lane road full of mansions overlooking Los Angeles. Just as her driver and another man in the passenger seat turn around to kill her, two drag racing cars from the opposite direction come crashing into the limo. Only the dark-haired woman survives. She works her way down the ridge to Sunset Boulevard and hides in a vacationing woman's apartment. Shortly after, Betty (Naomi Watts), the vacationing woman's niece, shows up at the apartment and runs into the dark haired woman, who now has amnesia. The bulk of the first part of the film is Betty and the dark haired woman trying to figure out who she is, why people were trying to kill her and why she had thousands of dollars and a strange key in her purse. This is interspersed with oddly surreal threads about Hollywood producers and directors, with occasional forays into a land of hoodlums and prostitutes.
The above may sound a bit complicated and disjointed, but that's not the half of it. The film is constructed so that the meaning will always be open to interpretation. It's basically guaranteed that you will not understand this film and you will not have very much confidence arriving at your own interpretation the first time around. Even if you have a lot of experience with like-minded films--such as Memento (2000), Donnie Darko (2001), The I Inside (2003) and The Butterfly Effect (2004)--you may not understand it on a second viewing, either. The studio was aware of this to the extent that they had director David Lynch write "10 clues to unlocking this thriller" and they put it on the back of the chapter listing insert in the DVD. Lynch being of a particular disposition, these clues are almost as cryptic as the film itself. It doesn't help when trying to figure it out in the early stages that the structure is extremely complex. It takes a very long time to figure out what parts are supposed to be "real" and there is a complex nesting of flashbacks in some sections, with only contextual clues that they're flashbacks.
But is the film worth watching, or worth trying to figure out? That depends on your tastes, obviously. On a surface level, the film is certainly attractive if you are a fan of surrealism, although it will tend to seem a bit slow and overly disjointed to some viewers. But those qualities, and many other surrealist aspects of the film, are typical of Lynch. A prime Lynchian moment is the old couple in the beginning bizarrely smiling almost as if they're alien pod people trying to put on a front. If you're familiar with that style and like it, you'll find much to love here, although in many ways, Mulholland Drive is fairly understated for Lynch. It's also worth noting, for viewers who'll primarily be interested in it or who enjoy it just as much as other aspects, that Mulholland Drive has a quite steamy lesbian scene. It's not gratuitous, although I have no problems with gratuitousness, but is instead an important hinge in the film.
Like all of Lynch's films, it's easy to become enraptured in his unique approach to every aspect of filmic art and his attention to detail. Any serious student of film (including "armchair students"/"cinephiles") should study Mulholland Drive; many will love it. Lynch doesn't let anything pass unmanipulated. He includes brilliant color schemes (such as the plethora of reds and pinks) with important symbolism. He makes unusual use of sound, such as the ringing telephone carrying over into the section of score that follows it (when Betty first arrives at the airport). He directs his actors to deliver their lines in a plethora of bizarre ways, such as his characteristic odd pauses. He lets his odd and surprising sense of humor poke through, such as the name "Winkie's", and the "Hot Dogs--made for Pinks" sign that provides a clue to some of the color symbolism.
Lynch's attention to detail in production design provides important, subtle clues throughout the film to help one unlock the meaning. It's interesting to note that Lynch even apparently demands that the DVD programming be unusual--there are no chapters on the disc; you must either watch the film in real time or fast forward or rewind to get back to particular points.
If the surrealism and veiled meaning of the film are attractive to you, or if you're just fond of "puzzles", then Mulholland Drive is well worth watching for that aspect. There is a fairly accepted interpretation of the film, at least on a broad, generalized level. I won't recount the standard interpretation here--it is worth researching, but only after you've seen the film a couple times and have reached your own conclusions. Many articles and monographs have been written on the film and interpretations; there are even websites dedicated to it.
For my money, however, although I generally love Lynch and find many things about Mulholland Drive attractive, it is not quite a 10 for me, at least not yet (I have a feeling that my score could still rise on subsequent viewings). To me, though, the "twist" aspect of the film is done much better in other works such as The I Inside and The Butterfly Effect. Mulholland Drive is more attractive to me for its surface surrealistic touches, but the plot doesn't carry them as well as some of Lynch's other films.
Still, Mulholland Drive is certainly recommended for the right crowd. If you're serious about film and do not mind having to think about what you watch (as if those two would not necessarily coincide), you shouldn't miss this one.