Genes encoding transcription factors are fundamental to developmental processes because their DNA-binding proteins can control expression of a multitude of genes. Therefore, activation of a single transcription factor gene can act as a genetic switch that controls the developmental destinies of groups of cells. Results of expression studies and mutational analyses in mice and Drosophila suggest an essential role in heart development for the homeobox class of transcription factor genes. Understanding the genetic circuitry of cardiogenesis will facilitate the identification of individuals with inherited cardiac diseases, and the possible prevention of these diseases with drug therapy or lifestyle modification. It may also allow for genetic counseling of affected individuals and family members and enable gene therapy aimed at correcting these defects.