Until recently, the lack of in vitro culture systems for elasmobranch models has been a major limitation for the use of these species in comparative functional genomics. Cold-water marine animals such as the little skate and dogfish shark are useful models for physiology and genomics, but homologous in vitro systems with which investigators can test hypotheses or confirm predictions at a molecular level are essential for widespread use of these models. Expression of elasmobranch genes in heterologous systems such as mammalian cell cultures or Xenopus oocytes may be compromised by differences in membrane lipid composition and missing or interfering accessory and messenger proteins. Heterologous systems are also not adaptable to mechanistic studies using genetically altered, dominant negative molecules. Another advantage derived from cell cultures from species such as shark and skate (that may be only seasonably available) is that they make biological material available yearround in any laboratory. Studies on regulation of gene expression in dogfish shark and little skate are beginning to benefit from the expanding genomic databases for these animals. Skate embryo-derived cell cultures also provide new avenues for elasmobranch research in embryology and organogenesis, toxicology, neurobiology, genome regulation and comparative stem cell biology.