Cleft palate only (CPO) is one of the most common congenital malformations worldwide. The etiopathogenesis of CPO is not completely understood. Environmental factors, such as smoking, alcohol consumption, intake of drugs during pregnancy, advanced paternal age, have been demonstrated to be a risk of CPO, but conflicting results have also been published. Insufficient intake of folic acid during the pregnancy has been suggested to increase the risk for CPO. The demonstrated risk for siblings and the higher risk for monozygotic twins suggest a genetic etiopathogenesis for CPO. In some cases of CPO a prevalent mode of inheritance has been reported, but oligogenic models with reduced penetrance, and the risk related to environmental factors have also been proved. One of the first manifestations associated with CPO is difficulty with feeding. Aerophagia is a problem in these infants with CPO and requires more frequent burping and slower feeding. The inability to generate intraoral breath pressure due to nasal air emission in CPO children frequently manifests as articulation difficulties, particularly consonant weakness, and unintelligible speech. Hearing disorders are prevalent among individuals with CPO, as a result of chronic otitis media with effusion due to eustachian tube dysfunction. A multidisciplinary team is essential to manage the many aspects of CPO. In treating CPO, the reconstructive surgeon works in cooperation with otolaryngologists, dentists and orthodontists, speech pathologists, audiologists, geneticists, psychiatrists, maxillofacial surgeons, social workers, and prosthodontists. CPO can be considered a genetically complex disease, but new knowledge and new therapeutic approaches have greatly improved the quality of life of these children. Prenatal diagnosis is an important step in the treatment of this disease.