The mammalian heart is the first functional organ, the first indicator of life. Its normal formation and function are essential for fetal life. Defects in heart formation lead to congenital heart defects, underscoring the finesse with which the heart is assembled. Understanding the reg-ulatory networks controlling heart development have led to significant insights into its lineage origins and morphogenesis and illuminated important aspects of mammalian embryology, while providing insights into human congenital heart disease. The mammalian heart has very little regenerative potential, and thus, any damage to the heart is life threatening and perma-nent. Knowledge of the developing heart is important for effective strategies of cardiac regen-eration, providing new hope for future treatments for heart disease. Although we still have an incomplete picture of the mechanisms controlling development of the mammalian heart, our current knowledge has important implications for embryology and better understanding of human heart disease. © 2013 Cold Spring Harbor Laboratory Press; all rights reserved.