Vitamin B₁₂ deficiency occurs in approximately 2% to 3% of adults in the United States. Risk factors include malabsorptive processes, limited dietary intake of vitamin B₁₂, use of certain medications (eg, metformin, proton pump inhibitors), and older age. Symptoms vary based on the severity of vitamin B₁₂ deficiency but may include fatigue, brain fog, depression, peripheral neuropathy, and ataxia. Although universal screening is not recommended, testing should be considered in patients with at least one risk factor for and one clinical feature of vitamin B₁₂ deficiency. Initial testing includes total serum vitamin B₁₂ level, which is diagnostic for deficiency if less than 180 pg/mL. Borderline levels (180–350 pg/mL) warrant a methylmalonic acid measurement, which is diagnostic for vitamin B₁₂ deficiency if elevated. Patients without a clear cause of deficiency should undergo further testing for atrophic gastritis with a Helicobacter pylori test and evaluation for autoantibodies associated with autoimmune gastritis. Oral vitamin B₁₂ supplementation can be used in most patients and is noninferior to intramuscular supplementation. Intramuscular administration should be considered in patients with severe deficiency or neurologic manifestations. Vitamin B₁₂ levels that are persistently elevated (greater than 1,000 pg/mL on two measurements) have been associated with solid tumors, hematologic malignancy, and increased risk of cardiovascular death.