We represent an update on diagnosing and treatment of vitamin B12 deficiency. Vitamin B12 deficiency should be suspected in all patients with unexplained anaemia and/or neurological symptoms,as well as in patients at risk of developing vitamin B12 deficiency such as the elderly and patients with intestinal diseases. Measurement of plasma cobalamins is suggested as the primary analysis followed by measurement of plasma methylmalonic acid in unsettled cases. Accumulating evidence indicates that the biologically active cobalamin,plasma holotranscobalamin (holoTC),may be superior to plasma cobalamins, and measurement of holoTC is currently introduced in the clinical setting. No consensus exists concerning evaluation of the cause for vitamin B12 deficiency,and pros and cons on the different tests mainly aiming at evaluation of the function of the gastric mucosa are presented. Once the diagnosis of vitamin B12 deficiency has been confirmed efficient treatment can be ensured either by injections every 2-3 month or by a daily dose of 1 mg vitamin B12.