This chapter discusses zebrafish to assess developmental neurotoxicity. Zebrafish have become a popular test species in toxicology, pharmacology and biomedical research. This chapter addresses several issues, results and research needs regarding the use of zebrafish to assess developmental neurotoxicity. Early development requires the coordinated, time-dependent participation of numerous genetic, biochemical and morphological processes that mold the physiology and behavior of an organism. Malformations and faulty cognitive development were also found in the offspring of mothers that had consumed fish contaminated with methylmercury. Early exposure to several drugs and environmental contaminants can cause adverse effects on a number of basic neurobiological functions, including sensory, motor and cognitive. Molecular biology has revealed the basic concordance of cellular events in a wide range of "lower" species including yeast, worms, flies and fishes. Zebrafish represent an attractive complementary species for developmental neurotoxicity assessments. Many have expressed an opinion that zebrafish would be appropriate for modeling diseases, for general toxicity testing and specifically for developmental neurotoxicity testing. Studies in zebrafish have emerged that are designed for rapid assessment of the potential of large numbers of chemicals to perturb the developing nervous system. These studies employ what are properly referred to as neurotoxicity screens. There have been numerous publications on the virtues of using zebrafish in at least three screening contexts: (1) environmental chemicals, (2) pharmaceuticals and (3) mutations. Screening for mutations has been primarily conducted to identify genes that may be involved in development and in disease. Although it is becoming clear that zebrafish larvae respond to neuroactive drug classes in ways resembling mammalian responses, very few studies have screened large numbers of chemicals for specific effects on the development of the nervous system. Zebrafish are now being used to discover novel pathways or mechanisms of toxicity, and possible treatments for various human diseases.