Henry Wallace broke with the Democratic Party in 1948. Anger with what Wallace considered Truman's dismantling of FDR's New Deal policies and a general slide back to the days before the Depression.
Wallace, running as a Third Party candidate (The Progressive Party), gave a series of radio talks leading up to the 1948 election which he based on subjects voters wanted to hear about the most. This talk, number 3 of a series of 7, is about Inflation and what could be done about it in 1948.
Henry Wallace: “Inflation, what you and I call the high cost of living, is not something that just happens like the weather. You can’t do anything about weather, but you can about inflation. Inflation is not accidental, it is man made. It is monopoly made. It was made and forced upon us by the men of Wall Street, acting through their agents; the Republicans and the Democrats – the two party’s. And there is something we can do about it. We can end it.”
Wallace was pretty much marginalized by the powers that be at the time. I suppose the closest comparison you could draw (although by no means a wholly accurate one) would be a 1948 version of Ralph Nader. Seen as a thorn in the side of the two party system and ignored to a great degree when he wasn't being smeared as a Communist sympathizer. It's always interesting to consider how things might have turned out had Wallace gained momentum. But you could also draw a conclusion as to how Third parties tended to fare in our political climate throughout history. Perhaps that's something to think about as November draws nearer in 2010.