The cardiovascular system is the first system that is developed in the embryo. The cardiovascular development is a complex process involving the coordination, differentiation, and interaction of distinct cell lineages to form the heart and the diverse array of arteries, veins, and capillaries required to supply oxygen and nutrients to all tissues. Embryonic stem cells have been proposed as an interesting model system to investigate molecular and cellular mechanisms involved in mammalian development. The present review is focused on extrinsic soluble factors, intrinsic transcription factors, receptors, signal transduction pathways, and genes regulating the development of cardiovascular system in vivo and in vitro. Special emphasis has been given to cardiovascular genomics including gene expression studies on the cardiovascular system under developmental and pathophysiological conditions.