Cobalamin (vitamin B12) deficiency in the elderly is an under recognized problem in daily clinical practice. It seems to be important because the deficiency of this vitamin can lead to irreversible neurological damage, anemia, osteoporosis, and cerebrovascular and cardiovascular diseases. Some clinical abnormalities that we thought were related to the normal aging changes may actually be caused by cobalamin deficiency, such as lack of ankle jerk reflex. The prevalence of cobalamin deficiency increases with age (ranges from 0.6% to 46% depending on the population studies and criteria for diagnosis). Other than clinical manifestations, there are some biomarkers for detection of cobalamin deficiency: the red blood cell mean corpuscular volume (MCV); serum cobalamin level; plasma holotranscobalamin; serum methylmalonic acid (MMA) levels and serum homocysteine levels. The interpretation and the application of these biomarkers are here presented.