Vitamin B12, or cobalamin (Cbl), deficiency can produce a number of neurologic complications, including myelopathy, peripheral neuropathy, optic neuropathy, and dementia. The myelopathy, combined systems disease, is probably the most well known manifestation, and is usually readily recognized. The frequency with which peripheral neuropathy is the sole presenting feature of Cbl deficiency is a point of controversy. The prevalence and the clinical and electrophysiologic features of Cbl deficiency peripheral neuropathy have not been well characterized. In addition, there is evidence that the commonly used assays of serum Cbl are not adequately sensitive. Testing the serum metabolites methylmalonic acid and homocysteine can increase the identification of Cbl deficient patients. Treatment with parenteral Cbl injections may not produce improvement of neurologic deficits, but might prevent worsening. In some patients with Cbl deficiency, oral Cbl may be an effective therapy.