Foxcl and Foxc2 are closelyrelated members ofthe Forkhead/Fox transcription factor family. The two Foxc genes have overlapping expression patterns in mesodermal and neural crest derivatives during development, as well as similar functions ofgene regulation. Consistently, mouse mutants for each gene have similar abnormalities in multiple embryonic tissues, including the eye, kidney and cardiovascular system. Analysis of compound Foxc1; Foxc2 mutant embryos reveals that the two Foxc genes have dose-dependent, cooperative roles in development. In particular, recent studies demonstrate that Foxcl and Foxc2 are essential for arterial cell specification , lymphatic vessel formation, angiogenesis and cardiac outflow tract development. This chapter will summarize and discuss current knowledge about the function ofFoxcl and Foxc2 in cardiovascular development.