What is the difference between blue and red serial numbers on US bills?

In 1928 the Treasury standardized the seal colors used on all US bills.

Blue seals were used for silver certificates. These bills were backed dollar-for-dollar with silver on deposit with the Treasury.

Red seals were used for United States Notes. These bills were issued directly by the Federal Government but had no precious metal backing them up.

Gold seals were used for gold certificates. These bills were backed dollar-for-dollar with gold on deposit with the Treasury.

Green seals were and are used for Federal Reserve Notes. FRNs are issued by the Federal Reserve Bank. Like US Notes, they're not backed by precious metal but instead by the "full faith and credit of the United States".

Production of gold certificated ended when the US went off the gold standard in 1933. Silver certificates were discontinued when silver was deregulated in the early 1960s. US Notes made up such a small fraction of all bills in circulation tht production was suspended in the late 1960s to save printing costs.