Myelomeningocele (MMC) is one of the most common anatomical malformations in humans. Children born with this malformation face a life with crippling disabilities, multiple surgical procedures, and complications. This is made all the more poignant as the majority of these children have normal intelligence. MMC is the result of a failure of the neural plates to fuse, leaving the developing spinal cord open to the amniotic fluid and unprotected from mechanical injury. This chronic chemical and mechanical trauma leads to destruction of the spinal cord. Pathological studies in humans and animals have demonstrated the progressive nature of this damage. Animal models of MMC have been created to simulate human MMC with success. In these models, early in utero coverage of the spinal defect preserves neurologic function at birth. In animal models the rescue of neurologic function can be accurately assessed by comparing animals that underwent repair to those that did not. In humans, there has been no accurate assessment of in utero neurologic function to allow outcome analysis of in utero repair. Open fetal surgery has been used to treat a number of lifethreatening malformations in human fetuses. However, there are many obstacles that must be overcome prior to human implementation. These challenges include patient selection criteria, operative techniques, and ethical dilemmas in performing fetal surgery for a nonlethal disease. We review the prospects for in utero repair of MMC and the challenges that remain prior to human implementation.