A muscularly-edited nonlinear structure is the main draw here, and it's important, for the story at the core of 21 Grams is simple: Three strangers are drawn together in the wake of a horrible car accident.
Iñárritu and his writer Guillermo Arriaga would rather you be unable to figure out anything during the first 15 minutes or so, until the fragmented scenes start coming together to form a plot of sorts, but it is nice to know from the above premise from the start; otherwise you might get so lost as to give up on the film.
I won't reveal how each stranger is involved in the accident, but you do have Sean Penn, Naomi Watts, and Benicio Del Toro as the three main characters. At various points, it appears that one of them is dying, two are in love, none know each other, and one is saving the other's life. This scattershot editing style works beautifully, actually, as it shows us how relationships between people can change so dramatically over time, which I think is the entire point of 21 Grams.
That said, once the film was over and I could piece together the events chronologically, the story is fairly weak. A crucial scene, where one character decides that the third must be killed, is so over-the-top that, though acted well, I'm thankful I didn't have to direct it. There would have been no subtle, real way to make it work. In the end it's a script problem. Iñárritu and Arriaga should have rethought it.
It's good to see Iñárritu retreat from the mania he exerted in his first film, the shrill and overrated Amores Perros, while still maintaining his style: the gritty, tinted handheld cinematography feels at home here, rather than merely self-conscious. And while Penn and Watts are winning all kinds of accolades for their good but ordinary performances, in my book it's Del Toro who should be getting all the attention. I suppose because he underplays it, the critics forget how good he is. But it's his character who is the most complicated, and it's his role which is the most difficult to pull off. He's great.