Klippel-Feil syndrome occurs in a heterogeneous group of patients unified only by the presence of a congenital defect in the formation or segmentation of the cervical spine. Numerous associated abnormalities of other organ systems may be present. This heterogeneity requires comprehensive evaluation of all patients and treatment regimes that can vary from modification of activities to extensive spinal surgeries. This also has made delineation of diagnostic and prognostic classes difficult and has complicated elucidation of the genetic etiology of the syndrome. Furthermore, it is unclear whether Klippel-Feil syndrome is a discrete entity, or if it is one point on a spectrum of congenital spinal deformities. Pedigree analysis has identified a human genetic locus for the disease. Mouse models suggest members of the PAX gene family and Notch signaling pathway as possible etiologic candidates. Only by identifying the link between the genetic etiology and the phenotypic pathoanatomy of Klippel-Feil syndrome will we be able to rationalize the heterogeneity of the syndrome.