A properly formed heart that contains a rhythmically contracting meshwork of myofibrils is essential for a healthy life. However, little is known about the molecular regulation of the morphogenetic processes that are involved in heart muscle development. Now, Risebro and colleagues report that the homeobox transcription factor Prox1 maintains muscle structure and growth in developing hearts (see p. 495). Cardiac-specific inactivation of Prox1 in mouse embryos, they show,disrupts the expression and localisation of several sarcomeric proteins (a sarcomere is the basic structural and functional unit of a myofibril) and results in abnormal myofibril organisation and growth-retarded hearts. Other experiments indicate that Prox1 directly regulates the expression of several sarcomeric structural proteins that help to coordinate heart contraction. Together, these results provide new insights into the molecular mechanisms that control the ultrastructure and growth of cardiac muscle during development. They also suggest that altered Prox1 expression might underlie some cardiomyopathies, diseases in which the heart muscle is weakened or structurally altered.