It is largely accepted that vertebrates are more susceptible to chemical insult during the early life stage. It is implied that if a chemical such as ethanol is developmentally toxic, it must interfere with, or modulate, critical signaling pathways. The probable molecular explanation for increased embryonic susceptibility is that collectively there is no other period of an animal's lifespan when the full repertoire of molecular signaling is active. Understanding the mechanism by which ethanol exposure disrupts vertebrate embryonic development is enormously challenging; it requires a thorough understanding of the normal molecular program to understand how transient ethanol exposure disrupts signaling and results in detrimental long-lasting effects. During the past several years, investigators have recognized the advantages of the zebrafish model to discover the signaling events that choreograph embryonic development. External development coupled with the numerous molecular and genetic methods make this model a valuable tool to unravel the mechanisms by which ethanol disrupts embryonic development. In this chapter we describe procedures used to evaluate and define the morphological, cellular and molecular responses to ethanol in zebrafish.