AbstractOrganogenesis of the vertebrate heart involves a complex sequence of events initiating with specification and differentiation of myocardial and endocardial cells in anterior lateral mesoderm shortly after gastrulation, followed by formation and rightward looping of the early heart tube. During looping, the heart tube elongates by addition of second heart field progenitor cells from adjacent pharyngeal mesoderm at the arterial and venous poles. Progressive differentiation is controlled by intercellular signaling events between pharyngeal mesoderm, foregut endoderm, and neural crest‐derived mesenchyme. Regulated patterns of myocardial gene expression and proliferation within the embryonic heart drive morphogenesis of atrial and ventricular chambers, while cardiac cushions, precursors of the definitive valves, form in the atrioventricular and outflow regions. In amniotes, separate systemic and pulmonary circulatory systems arise by septation and remodeling events that divide the atria and ventricles into left and right chambers. Cardiac neural crest cells play a key role in dividing the arterial pole of the heart into the ascending aorta and pulmonary trunk. During the remodeling phase the definitive cardiac conduction system, that coordinates the heartbeat, is established. In addition, the epicardium, critical for regulated ventricular growth and development of the coronary vasculature, spreads over the surface of the heart as an epithelium from which cells invade the myocardium to give rise to diverse cell types including fibroblasts and smooth muscle cells. Cardiogenesis thus involves highly coordinated development of multiple cell types and insight into the different lineage contributions and molecular regulation of each of these steps is expanding rapidly.WIREs Dev Biol2013, 2:17–29. doi: 10.1002/wdev.68This article is categorized under:Vertebrate Organogenesis > Musculoskeletal and Vascular