Analysis of the phylogenetically ancientNK-2class of homeobox genes has opened up an entirely new approach to molecular, genetic, and biochemical analysis of early heart development. TheDrosophila NK-2homeobox genetinmanplays 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.tinmanhomologues 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 thetinexpression 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 ofDrosophila.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 ofNKclass homeobox genes will be reviewed, emphasizing and contrasting the roles oftinmanandNkx2-5in heart development.