Research on embryonic development and differentiation provides a sensitive, but challenging opportunity to use a variety of techniques designed to modulate gene expression. Changes in the expression of a single gene can alter levels of other genes and provide information on developmentally regulated gene expression pathways. The morphological consequences of altered gene expression can link gene expression to developmental fate. Oligonucleotide-based approaches offer a variety of means to potentially disrupt normal gene expression. The basis for some of these approaches is presented in this review.