Cadherins are cell surface adhesion molecules that play important roles in development of vertebrate tissues and organs. We studied cadherin2 expression in developing zebrafish heart using in situ hybridization and immunocytochemical methods and we found that cadherin2 was strongly expressed by the myocardium of the embryonic zebrafish. To gain insight into the role of cadherin2 in the formation and function of the heart, we analyzed cardiac differentiation and performance in a cadherin2 mutant, glass onion (glo). We found that the cadherin2 mutant had enlarged pericardial cavity, disorganized atrium and ventricle, and reduced expression of a ventricular specific marker vmhc. Individual myocardiocytes in the glo mutant embryos become round shaped and loosely aggregated. In vivo measurements of cardiac performance reveal that the mutant heart has significantly reduced heart rate, stroke volume and cardiac output compared to control embryos. Formation of the embryonic vascular system in the glo mutants is also affected. Our results suggest that cadherin2 plays an essential role in zebrafish cardiovascular development.