On the one hand, it's not so surprising that Lee Hamilton would endorse Barack Obama. Obama's foreign policy team consists of several former Hamilton staffers, and Obama himself seems to embody Hamilton's foreign policy sensibility. (See this recent piece for more on that.)
On the other hand, the Hamilton endorsement is actually pretty telling. While working on the piece I just linked to--this would have been in late February--I asked one of Obama's foreign policy advisers why, if the two men were on such similar wavelengths, Hamilton hadn't already endorsed Obama. The aide told me that Hamilton had a policy of not endorsing in presidential primaries because of his position as head of the Woodrow Wilson Center, which made it important for him to be on good terms with either potential White House occupant. (Not entirely sure why he felt better about endorsing in a general election--presumably because he's a former Democratic congressman, so it's not like his partisan sympathies are a secret...)
I mention this because now that Hamilton is endorsing, it must mean that either: a.) He feels like the nomination contest is essentially over, or b.) He feels like the risk to the party of letting it go on and on outweighs the risk to him of getting on the wrong side of an incoming administration. Either way (or both), I think that makes his announcement especially significant.