This review outlines the nature of inter-individual variation in trace element bioavailability, focusing on genetic and epigenetic determinants. We note that pathogenic mutations responsible for dangerously high (or low) status for the micronutrient are unlikely to make large contributions to variability in bioavailability among the general population. Prospective genotyping (for variants in genes encoding selenoproteins) of participants in human studies illustrate one approach to understanding the complex interactions between genotype and trace element supply, which determine the functional bioavailability of selenium. Rapid advances in technological and bioinformatics tools; e. g., as used in Genome-Wide Association Studies, are opening new avenues for research on the genetic determinants of inter-individual variation in trace element bioavailability. This may include copy number variants in addition to the more widely studied polymorphisms. Future research on trace element bioavailability should encompass studies of epigenetic variants, including the role of non-coding (micro) RNA.