Analysis of the phylogenetically ancient NK-2 class of homeobox genes has opened up an entirely new approach to molecular, genetic, and biochemical analysis of early heart development. The Drosophila NK-2 homeobox gene tinman plays an essential role in segregating cardiac and visceral muscle potentiality, as well as that of some somatic muscles, in nascent mesoderm of the fly embryo. In its absence, precursor cells for these muscles do not form. tinman homologues have now been isolated from vertebrate genomes and at least one of them, Nkx2-5, is expressed in heart progenitor cells and is essential for myogenic and morphogenetic differentiation of the mammalian heart. Signaling pathways that establish the tin expression domain also appear to be conserved in vertebrates. These findings suggest that heart development in flies and vertebrates utilize similar genetic pathways and engender optimism that the dissection of mammalian heart development will profoundly profit from the rich genetics of Drosophila. The findings also prompt the questions: are the hearts of vertebrates and invertebrates actually homologous, and how much can we learn from the comparative approach? In the sections below, the structure, regulation, function, and evolution of NK class homeobox genes will be reviewed, emphasizing and contrasting the roles of tinman and Nkx2-5 in heart development.