Spina bifida is the most common and complex central nervous system malformation in humans. Management of these patients involves various disciplines to ensure the best possible outcome achieved and provide a good quality of life for its patients [1, 2]. The study of this condition is extremely relevant in that even in the 20 years since the discovery of the benefits of folic acid this condition is highly prevalent around the world and its occurrence does not seem to decrease . Interestingly, the debate is very much ongoing upon the evidence that the United States of America has seen a decline in cases of spina bifida (https://www.cdc.gov/ncbddd/spinabifidadata.html). This review paper intends to compare and contrast spina bifida in humans and spina bifida in the mouse, which is the leading animal model of this devastating condition in light of the information studies on animal models have shed on the human counterpart [4–6].