I know I'm very late to the Trent Lott pile-on, but anyone who praises Strom Thurmond's 1948 segregationist campaign deserves what he gets.
Josh Marshall has broken much of the story, including laying out Lott's record of neo-Confederate activism in excrutiating detail. (Liberal blogger Atrios has also come up with some good nuggets.) Just as noteworthy, the clamor for Lott to go has ben led by conservative bloggers and media (see the last week's worth of posting on InstaPundit and Andrew Sullivan for most of the appropriate links.) Some of the best pieces have come from National Review Online - click here, here and here for examples.
Probably the most eloquent explanation of why Lott must go was provided by Charles Krauthammer:

This is not just the kind of eruption of moronic bias or racial insensitivity that cost baseball executive Al Campanis and sports commentator Jimmy the Greek Snyder their careers. This is something far more important. This is about getting wrong the most important political phenomenon in the past half-century of American history: the civil rights movement. Getting wrong its importance is not an issue of political correctness. It is evidence of a historical blindness that is utterly disqualifying for national office.

Josh Marshall and others have raised the troubling point about Lott's history:

The truth is that everyone who's sentient and even remotely keeps up on politics has known about this stuff for years -- at least since the last Trent Lott-segregation scandal broke back in late 1998. Sad to say, everyone just agreed not to pay attention, not to care.

Why, in fact, did this latest gaffe erupt and hopefully end Lott's career as a political leader, while his awful history did not? Why was this the last straw?
I can think of a couple of contributing factors:
1) Lott's case reminds me a lot of Pat Buchanan's gradual implosion in respectability over the last decade. For years, there was copious evidence of Buchanan's bigotry, but the DC political-media establishment couldn't emotionally comprehend that the nice man they dealt with regularly actually believed such hateful things. Eventually, the evidence became too great to ignore.
2) For better or (mostly) worse, the majority of the American body politic will put up with a certain amount of mud-wallowing to get elected. Such a candidate may earn a certain amount of amnesty if he: a) goes through some motion of repudiation and b) signals that on some level, he doesn't really believe in the merits of the objectionable beliefs. (This is the obverse of Paul Krugman's column today; the objectionable candidates also have to signal to the more tolerant majority that they don't really believe in the objectionable tactics they're using.) Lott repudiated the CCC group in the past, grudgingly though it was. When he then makes the statement at thurmond's party, in a non-campaigning context, it dispells any disavowals he has ever made and recasts all his prior objectionable acitivities - as evidence of his beliefs rather than mere tactics. That's why Trent Lott looks much different now than he did last week.
As Josh Marshall noted:

Much of the wobbly coverage of this story (and much of the deep unease over this among conservatives) stems from fact that this obviously wasn't some misstatement or hyperbole or slip of the tongue. It's what the guy believes. You can tell that from just listening to his words. And it's clear from the man's long history of hobnobbing with neo-confederate wing-nuts and general nostalgia for the pre-civil-rights era South. It's even painfully, and belatedly, clear from his weird unwillingness to utter even a pro forma condemnation of segregation. It's what the guy believes.

Hopefully Lott will resign this afternoon.