This chapter deals with the genetics of congenital malformations of craniofacial region. The chapter begins with the genetics of embryological development of face. Genes controlling the normal formation of frontonasal process (Shh, FGF-8 and retinoic acid), maxillary and mandibular processes (FGF-8, Msx-1, BMP 4/7) are described in detail. Genes involved in the common ectodermal dysplasia (EDA, EDAR, EDARDD, GJB6, p63) and their mechanism of action is discussed. Holoprosencephaly is caused by a large number of genes (SIX, SHH, TGIF, ZIC2, PTH1, TTF1 and GLI 2). The TCOF1 gene codes for protein called treacle which is required for normal craniofacial development. The mutation of this gene leads to Treacher Collin syndrome. The cleidocranial dysplasia, which is caused due to mutation in CBFA1 gene, plays an important role in development of bone and cartilage differentiation. Chapter discusses the mutation of FGFR2 gene which causes Apert syndrome and Crouzon syndrome. This chapter also deals with the genetics of Gorlin-goltz syndrome, Waardenburg syndrome and Osteogenesis imperfecta.