In this issue, Ali-Khan et al. (pages 139–152) have used gene expression analysis to elucidate signaling pathways potentially involved in the mechanism of the developmental toxicity of excess vitamin A (retinol acetate). The ability to examine simultaneously the expression of thousands of genes in a tissue of interest has emerged relatively recently. While some have characterized the use of this technology to elucidate mechanisms of toxicity as “fishing trips,” the approach can be powerful for generating hypotheses. Global gene array analysis has been used to some success in identifying developmental pathways affected by the human and murine teratogen, valproic acid (Kultima et al., 2004; Okada and Fujiwara, 2006), and has also been used for expression profiling across normal developmental stages (e.g., Bonner et al., 2003; Gheorghe et al., 2006; Wang et al., 2005). Here, the experimental model is the murine limb exposed to retinol while developing in vitro. The premise is straightforward; by examining changes in the embryonal transcriptome in response to developmental insult, one can formulate hypotheses as to the developmental pathways that are critically affected.