Vitamin B12 deficiency may be underestimated in the general population. High-risk groups for the deficiency syndrome include the elderly, patients taking ulcer medications over long periods, patients with acquired immunodeficiency syndrome, vegetarians, patients who have undergone stomach resection or small bowel resection, or both, and patients with dementia. The vitamin B12 deficiency syndrome is characterized by five stages, the fifth of which results in irreversible neuropsychiatric manifestations. Although the deficiency is easily treated, diagnosis is somewhat complicated by the shortcomings of the various tests. Current state-of-the-art testing uses serum cobalamin levels as a screening test and serum or urine homocysteine and methylmalonic acid determinations as confirmatory tests. Vitamin B12 deficiency is treatable with monthly injections, large doses of daily oral supplement tablets, or an intranasal gel, which is far better absorbed than comparable oral supplements.