Vitamin B-6 encompasses a group of related compounds (vitamers) that can only be biosynthesised de novo by plants and microorganisms. Enzymatic cofactor and antioxidant functions for vitamin B-6 are established in all kingdoms. Human vitamin B-6 dietary insufficiency or genetic defects in B-6 vitamer interconversion result in various neurological and inflammatory pathologies with several populations at-risk or marginal for vitamin B-6 status. Three (rice, wheat and cassava) of the world's top five staple crops do not meet the recommended dietary allowance for vitamin B-6, when consumed as a major proportion of the diet. In addition, controlled enhancement of the appropriate B-6 vitamer in crops has the potential to confer stress resistance. Thus, crop biofortification strategies represent an opportunity to reduce the risk of deficiency in populations with limited diet diversity and quality, as well as improving stress tolerance.