The cause and effect relationship between environmental factors, including toxins (naturally occuring) and toxicants (man-made environmental contaminants), and neural tube defects is well-established. More recent evidence has demonstrated a requirement for the claudin family of tight junction proteins in regulating epithelial remodelling events that transform the plate neural plate into a closed tube. At the molecular level, toxicants are known to disrupt claudin expression and tight junction barrier function. In this review we consider the evidence leading to the hypothesis that toxins and toxicants affect neural tube closure due to their effects on the claudin family of tight junction proteins.