Vitamin B12 (B-12) deficiency is still relatively common in low-, medium-, and high-income countries, mainly because of dietary inadequacy and, to a lesser extent, malabsorption. This narrative review is based on a systematic search of evidence on methods to assess B-12 bioavailability and technologies to enhance its absorption. A total of 2523 scientific articles identified in PubMed and 1572 patents identified in Orbit Intelligence were prescreened. Among the reviewed methods, Schilling's test and/or its food-based version (using cobalamin-labeled egg yolk) were used for decades but have been discontinued, largely because they required radioactive cobalt. The qualitative CobaSorb test, based on changes in circulating holo-transcobalamin before and after B-12 administration, and the 14C-labeled B-12 test for quantitative measurement of absorption of a low-dose radioactive tracer are currently the best available methods. Various forms of B-12 co-formulated with chemical enhancers (ie, salcaprozate sodium, 8-amino caprylate) or supplied via biotechnological methods (ie, microbiological techniques, plant cells expressing cobalamin binding proteins), encapsulation techniques (ie, emulsions, use of chitosan particles), and alternative routes of administration (ie, intranasal, transdermal administration) were identified as potential technologies to enhance B-12 absorption in humans. However, in most cases the evidence of absorption enhancement is limited.