Orofacial syndromes are a heterogeneous group of disorders with variously expressed anomalies especially in the craniofacial, but also other regions. With greater knowledge of genetics, it has become evident that the syndromes inherited according to Mendel's laws are rare and that most of them are inherited multifactorialy, where, in addition to the influence of one or more genes, the development of malformations is also influenced by environmental factors. The most common syndromes of the orofacial region caused by anomalies of chromosomes are Down syndrome, Klinefelter syndrome, Turner syndrome, Patau syndrome, Fra-X syndrome and Treacher Collins syndrome. Dysmetabolic syndromes arise from genetic disorders of enzymatic proteins, with the main representatives being mucopolysaccharoses and mucolipidosis. Dysplastic syndromes are a group characterized by abnormal cell structure in tissues and can be classified as simple or hamartoplastic syndromes. Simple dysplastic syndromes involve a single germ layer and are categorized as ectodermal and mesodermal dysplasias. Hamartoplastic syndromes affect one, two or three germ layers, and are characterized by the appearance of hamartomas, tissue hyperplasia and a tendency to develop neoplasia. Cleft lip and/or palate are the most common congenital malformation of the orofacial region that can occur independently or within syndromes, such as DiGeorge and van der Woude syndrome. Syndromes caused by immune anomalies that most offten affect the orofacial region are Behçet's and Sjögren's syndrome. Other well-known syndromes affecting the orofacial region include Gorlin-Goltz syndrome, cleidocranial dysplasia and Murray-Puretić syndrome. Knowledge of syndromes is vital for ensuring optimal oral and general health of an individual.