We have developed a loss-of-function model for Gata4 in zebrafish, in order to examine broadly its requirement for organogenesis. We show that the function of Gata4 in zebrafish heart development is well conserved with that in mouse, and that, in addition, Gata4 is required for development of the intestine, liver, pancreas and swim bladder. Therefore, a single transcription factor regulates the formation of many organs. Gata6 is a closely related transcription factor with an overlapping expression pattern. We show that zebrafish depleted of Gata6 show defects in liver bud growth similar to mouse Gata6 mutants and zebrafish Gata4 morphants, and that zebrafish embryos depleted of both Gata4 and Gata6 display an earlier block in liver development, and thus completely lack liver buds. Therefore, Gata4 and Gata6 have distinct non-redundant functions in cardiac morphogenesis, but are redundant for an early step of liver development. In addition, both Gata4 and Gata6 are essential and non-redundant for liver growth following initial budding.