Holoprosencephaly (HPE) is considered the leading abnormality of the brain and face in humans and is frequently associated with a wide spectrum of specific craniofacial anomalies including mid-line facial clefts, cyclopia and nasal irregularities. A standard course of treatment has not been developed and management is symptomatic and supportive. In this work, the authors discuss the wide-ranging spectrum of HPE and propose surgical guidelines to provide more uniform and appropriate care to patients suffering from holoprosencephaly. Assessment of the patient’s brain abnormality is essential in determining the extent and benefit of surgical intervention. The authors discuss a median straight-line repair of the lip and repair of the anterior palate in a one-year old female and review the risks and benefits of surgery. Consistent with the ethical approach of surgical beneficence, the authors recommend intervention at the earliest possible time.