Way back in 2005, I noted that "the American people do not elect Senators to the Presidency...Since Amendment XVII redefined the Senate in 1913, only two Presidents have been elected whose highest political qualification was service in the Senate: Warren G. Harding and John F. Kennedy."
On the democratic side, all three of the candidates with a shot at the nomination (sorry, Dennis) fall into that category. On the Republican side, a recent national poll puts McCain just ahead of Huckabee. There's a chance the general election could come down to two contenders from the Senate.
If the Republicans select Huckabee or Romney, Democrats who know history might sweat a bit: a Senator hasn't beat a governor in a presidential election since Harding beat James Cox in 1920. (Cox's running mate, Franklin D. Roosevelt, went on to some success in politics after this defeat - an example that might hearten John Edwards.) It's worth noting that 1920 was the first election after the ratification of the Nineteenth Amendment, which extended the franchise to women - and Harding took the female vote by a huge margin. (Why? Perhaps because the Republicans did a better job of registering their female supporters in the few months between ratification and the election. Also it didn't hurt that Harding could claim to have directly supported the Amendment.)
Of course, this election is already an oddity, the first time since the 1952 Eisenhower/Stevenson race that there's not a sitting President or Vice-President in the running.