Clinical genetics is a medical discipline that uses the basic principles of Mendelian and human genetics to evaluate and diagnose children to determine if a patient has an underlying genetic cause for his or her congenital anomalies and/or phenotypic differences. In a child with cleft palate (CP) and/or velopharyngeal dysfunction (VPD), this medical evaluation often looks for the presence of additional features that could indicate the possibility of an underlying genetic syndrome. Genetics professionals conduct a specialized physical examination focusing on dysmorphology and, with the help of genetic counselors, collect a detailed family history. A genetic diagnosis is most often made with specialized laboratory testing on peripheral blood. Genetic tests have limitations, and expertise is required for interpretation. A genetic diagnosis may have clinical utility in the form of change in medical treatment, change in management/surveillance, prognostication, or recurrence risk counseling. CP is found in many different genetic syndromes, including both chromosomal and single gene disorders. There have been fewer investigations into genetic etiologies for VPD; however, preliminary information shows that 22q11.2 deletion syndrome stands out as the most commonly identified genetic cause. Much of the human genome remains uncharted territory, and new gene discoveries are made every year, making it likely that many new genes that cause and/or contribute to the development of CP and VPD will be identified in the future. Health care providers who care for children with CP and VPD should have familiarity with the more common genetic conditions they may encounter and the breadth of possible genetic etiologies.