Cleft lip and palate (CLP) are common birth defects with complex genetic and environmental causes. While syndromic CLP has been well studied, non-syndromic CLP remains poorly understood. Recent research using epidemiology, phenotyping, genome-wide association studies (GWAS), and animal models has identified several genetic and environmental risk factors for non-syndromic CLP. These findings enhance understanding of developmental biology and offer new opportunities for clinical research. CLP affects approximately 1 in 700 live births, with variations across populations and environmental factors. Non-syndromic CLP accounts for about 70% of cases, while syndromic forms involve other malformation syndromes. Genetic studies have identified several loci associated with CLP, including IRF6, MAFB, ABCA4, VAX1, and Wnt signaling pathways. Environmental factors such as maternal smoking, alcohol consumption, and nutritional deficiencies also contribute to CLP risk. Gene-environment interactions are important in CLP, and future research aims to integrate genetic and environmental risk factors to improve prevention and treatment. Advances in genomics and imaging are helping to identify sub-clinical phenotypes that may contribute to CLP. Overall, understanding the genetic and environmental factors underlying CLP is crucial for improving clinical care and prevention strategies.Cleft lip and palate (CLP) are common birth defects with complex genetic and environmental causes. While syndromic CLP has been well studied, non-syndromic CLP remains poorly understood. Recent research using epidemiology, phenotyping, genome-wide association studies (GWAS), and animal models has identified several genetic and environmental risk factors for non-syndromic CLP. These findings enhance understanding of developmental biology and offer new opportunities for clinical research. CLP affects approximately 1 in 700 live births, with variations across populations and environmental factors. Non-syndromic CLP accounts for about 70% of cases, while syndromic forms involve other malformation syndromes. Genetic studies have identified several loci associated with CLP, including IRF6, MAFB, ABCA4, VAX1, and Wnt signaling pathways. Environmental factors such as maternal smoking, alcohol consumption, and nutritional deficiencies also contribute to CLP risk. Gene-environment interactions are important in CLP, and future research aims to integrate genetic and environmental risk factors to improve prevention and treatment. Advances in genomics and imaging are helping to identify sub-clinical phenotypes that may contribute to CLP. Overall, understanding the genetic and environmental factors underlying CLP is crucial for improving clinical care and prevention strategies.