Formation of the heart is dependent on an intricate cascade of developmental decisions. Analysis of the molecules and mechanisms involved in the specification of cardiac cell fates, differentiation and diversification of cardiac muscle cells, and morphogenesis and patterning of different cardiac cell types has revealed an evolutionarily conserved network of signaling pathways and transcription factors that underlies these processes. The regulatory network that controls the formation of the primitive heart in fruit flies has been elaborated upon to form the complex multichambered heart of mammals. We compare and contrast the mechanisms involved in heart formation in fruit flies and mammals in the context of a network of transcriptional interactions and point to unresolved questions for the future.