Byron Dorgan to retire. Dorgan has been the consensus most popular pol in North Dakota for decades, and originally won his Senate seat in 1992.
It's hard to believe that the Dems can keep this seat; their best bet is probably Earl Pomeroy, who as a Member of Congress represents the entire state, but he won't be favored even if he runs. North Dakota, which practically never goes for a Democrat for President, has been represented by two Democrats in the Senate since 1987. It's a little tricky...North Dakota mostly had nothing but Republican Senators from statehood through 1960, when Democrat Quentin Burdick was elected (by the way: I worked for Burdick, long ago). Then, in 1986, Kent Conrad defeated Senator Mark Andrews, to make it a solid Democratic delegation. Conrad actually retired, with then-Member of the House Dorgan winning his seat in 1992, but meanwhile Burdick died, and Conrad wound up running for and winning Burdick's seat, thus becoming a trivia answer.
So, not only is this a short-term loss for the Dems, but it's most likely a long-term loss, too. It's always been a bit of a fluke that the Democrats managed to hold both these seats, and the odds are that this one will be pretty hard for them to recover if they lose it now.