Many developmental processes are highly conserved in all vertebrate organisms. This conservation has allowed developmental biologists to use numerous animal models to further our understanding of the molecular mechanisms that govern heart development and congenital heart disease. Amphibian embryos represent a useful model for such studies because their relatively large embryos are available in large numbers and survive simple microsurgery. In addition, until swimming tadpole stages, an amphibian embryo develops using nutrients stored in each of its many cells. This feature has the advantage that explants isolated from embryonic tissue will continue to survive in isolation and differentiate in culture. Furthermore, cells from the ectodermal layer of the blastula or gastrula embryos are stem cell like in that they are pluripotent and can be induced to form various tissues in vitro. Here, we will review work from recent studies in which explants from the amphibian embryos were used to further our understanding of vertebrate heart development. We will bring together the key facts needed for using Xenopus explants as experimental approaches for studying molecular pathways and gene regulatory networks in vertebrate cardiogenesis. The knowledge generated with these approaches supports the usefulness of amphibian explants, and the relevance of the findings strongly validates the conservation of molecular pathways that underlie heart development in all vertebrates.