Over the past decade, the use of gene expression profiling (i.e., toxicogenomics or transcriptomics) has been established as the vanguard "omics" technology to investigate exposure-induced molecular changes that underlie the development of disease. As this technology quickly advances, researchers are striving to keep pace in grasping the complexity of toxicogenomic response while at the same time determine its applicability for the field of developmental toxicology. Initial studies suggest toxicogenomics to be a promising tool for multiple types of study designs, including exposure-response investigations (dose and duration), chemical classification, and model comparisons. In this review, we examine the use of toxicogenomics in developmental toxicology, discussing biological and technical factors that influence response and interpretation. Additionally, we provide a framework to guide toxicogenomic investigations in the field of developmental toxicology.