High-throughput phenotypic drug discovery using Xenopus embryos. The flowchart shows the steps involved in phenotypic chemical screening. Once embryos have reached the desired embryonic stage, they are arrayed in 48-well plates and treated with single compounds taken from the chemical library of choice. In the primary screen, embryos are scored visually by bright-field microscopy for the desired developmental phenotype(s) or morphological change(s). Positive hits are verified by repeating the primary chemical screen. In the secondary screen, embryos are treated with verified compounds and subsequently analyzed by whole-mount in situ hybridization or immunohistochemistry. Figure adapted from Kälin et al. (2009).