Who gives a fuck?
"What the hell? Is the sky still blue?
As a general rule, do not use the serial/Oxford comma: so write 'a, b and c' not 'a, b, and c'. But when a comma would assist in the meaning of the sentence or helps to resolve ambiguity, it can be used -- especially where one of the items in the list is already joined by 'and'.
The kottke.org style guide still advocates the use of the Oxford comma, but take that with a grain of salt; I also misuse semicolons, use too many (often unnecessary) parentheses -- not to mention m-dashes that are actually rendered as two n-dashes in old-school ASCII fashion -- use too many commas, and place punctuation outside quotation marks, which many people find, in the words of Bill S. Preston Esq. and Ted "Theodore" Logan, "bogus". Oh, and in another nod to the old-school, I also use "dumb quotes" instead of the fancier and, I guess, technically more correct "smart quotes". (via, who else?, @tcarmody (or should that be "whom else?"))
Update: The document I linked to above is from a branding style guide for Oxford University. It recommends against using the Oxford comma in most cases. The Oxford Style Manual, meant for the general public and last published in 2003 by Oxford University Press, "a department of the University of Oxford", recommends using the Oxford comma in all cases. So basically, Oxford is telling us to use the Oxford comma but isn't going to use it internally. Oxford gone schizo, y'all! (thx, @rchrd_h)
Update: Further clarification comes in the form of this official statement from Oxford University Press...they are definitely in favor of the Oxford comma."