Mutations may be tolerated without noticeable effect or may present with a specific phenotype that reveals information about the function of the mutated gene. This information is an inexhaustible source for understanding biology and let us ask particular questions about the molecular mechanisms of development, degeneration and disease. The zebrafish (Danio rerio) has been proven to be instrumental in the genetic analysis of spontaneous and induced mutations and has provided invaluable clues to the elucidation of complex molecular processes in vertebrate biology. Since completion of the two large-scale mutagenesis screens carried out at the Max-Planck Institute in Tuebingen and at the Massachusetts General Hospital in Boston, many of the recovered mutations have been cloned and the function of the mutated genes studied. Special interest laid in the analysis of mutations affecting structures and organ systems characteristic for vertebrates such as the notochord, neural crest, heart, vasculature, blood and kidney. This review updates our knowledge of heart, vessel, blood and kidney organogenesis in zebrafish and extrapolates our insights to human disorders by assessing common genetic pathways.