The Washington Post is reporting that White House Chief of Staff Andrew H. Card, Jr. announced his resignation this morning, effective April 14th. He will be replaced by Joshua B. Bolten who currently serves as director of the Office of Management and Budget.
Card has been President Bush's Chief of Staff since the beginning of the president's first term in 2001 and has served longer than any person in that position since Sherman Adams under President Eisenhower.
Wikipedia has short biographies on Card and Bolten.
Speculation: Card is leaving to play a significant role in the presidential campaign of Massachusetts Governor Mitt Romney.