Summary Vitamin B₁₂ deficiency, mostly of maternal origin in newborns, is a well treatable condition but can cause severe neurologic sequelae. In women of childbearing age and pregnant women worldwide vitamin B₁₂ deficiency has been reported with frequencies of 10%–50%. Children with vitamin B₁₂ deficiency are asymptomatic at birth but may develop severe multisystemic symptoms, including irreversible developmental impairment in the second half-year of life. Early detection of vitamin B₁₂ deficiency allows for presymptomatic treatment. This article provides an overview over the function of vitamin B₁₂ and discusses causes and frequency of vitamin B₁₂ deficiency in newborns, infants, and women of childbearing age. It describes novel successful approaches to newborn screening (NBS) for vitamin B₁₂ deficiency and results of a pilot study which performed systematic NBS for vitamin B₁₂ deficiency using so-called second-tier strategies by measuring homocysteine and methylmalonic acid in dried blood spots. Recommendations for diagnostics in mothers of children with vitamin B₁₂ deficiency are described as well as results of systematic work-up in mothers and treatment and follow-up of children with vitamin B₁₂ deficiency detected by NBS. Treatment options of vitamin B₁₂ deficiency are presented including a newly developed standardized supplementation scheme with exclusively oral vitamin B₁₂ supplementation. Recommendations for preventive approaches to vitamin B₁₂ deficiency for children and mothers are stated. Many children worldwide could benefit from systematic inclusion of vitamin B₁₂ deficiency into NBS panels. In addition, preventive approaches to maternal vitamin B₁₂ deficiency should be implemented systematically during maternal care.