The developing heart forms during the early stages of embryogenesis, and misregulated heart development results in congenital heart defects (CHDs). To understand the molecular basis of CHDs, a deep understanding of the morphological and genetic basis of heart development is necessary. Atrial Natriuretic Factor (ANF) is an important and extremely sensitive marker for specific regions of the developing heart, as well as for disturbances in the patterning of the heart. This review summarizes the dynamic expression of ANF in the developing heart and its usefulness in understanding the early molecular defects underlying CHDs.