Cleft lip and palate is a common human birth defect, and its causes are being dissected through studies of human populations and through the use of animal models. Mouse models in particular have made a substantial contribution to our understanding of the gene pathways involved in palate development and the nature of signaling molecules that act in a tissue-specific manner at critical stages of embryogenesis. Related work has provided further support for investigating the role of common environmental triggers as causal covariates.