Pernicious anemia, an extreme form of vitamin B12-deficiency, was most likely first portrayed in 1822 by James Combe, a Scottish physician from Edinburgh. Vitamin B12 in the liver extract was able to enhance the growth of the bacteria, and the growth rate could be used as a measure of the amount of the unknown factor in the extract. Vitamin B12 is essential for cell growth and replication and participates in transmethylation reactions during the synthesis of methionine, choline, creatinine and nucleic acids. To understand the feasibility of oral vitamin B12-treatment it is necessary to recognize the clinical pharmacology of vitamin B12, which is quite complex. Oral supplementation reduces the risk of injection complications such as infections or cyst formations and nerve injuries are avoided. Vitamin B12-treatment was from the very beginning not just a matter of clinical effectiveness, but also cost-effectiveness.