Vitamin B(12) (B(12)) is a rare and vital micronutrient for which mammals have developed a complex and highly efficient dietary uptake system. This uptake pathway consists of a series of proteins and receptors, and has been utilized to deliver several bioactive and/or imaging molecules from (99m)Tc to insulin. The current field of B(12)-based drug delivery is reviewed, including recent highlights surrounding the very pathway itself. Despite over 30 years of work, no B(12)-based drug delivery conjugate has reached the market-place, hampered by issues such as limited uptake capacity, gastrointestinal degradation of the conjugate or high background uptake by healthy tissues. Variability in dose response among individuals, especially across ageing populations and slow oral uptake (several hours), has also slowed development and interest. This review is intended to stress again the great potential, as yet not fully realized, for B(12)-based therapeutics, tumor imaging and oral drug delivery. This review discusses recent reports that demonstrate that the issues noted above can be overcome and need not be seen as negating the great potential of B(12) in the drug delivery field.