Central nervous system defects including hydrocephalus are rare in cases of VACTERL association. However, recent reports suggest that there may be one or more disorders in which this combination of anomalies occurs. We report 8 additional patients including a recurrence in a previously described family, review the literature, and provide some population-based data of VACTERL-type anomalies in hydrocephalus cases. VACTERL with hydrocephalus appears distinct from hydrolethalus and similar conditions but is itself heterogeneous. The pattern of inheritance of the disorders involved is unclear, but autosomal recessive and sex-linked forms likely occur. The prognosis of VACTERL cases with hydrocephalus appears much poorer than for those with classic VACTERL anomalies, and the recurrence risk may be higher than for either the VACTERL association or isolated hydrocephalus.