We aimed to synthesize the recent work on the intra-vertebral heterogeneity in density, trabecular architecture and mechanical properties, its implications for fracture risk, its association with degeneration of the intervertebral discs, and its implications for implant design. As compared to the peripheral regions of the centrum, the central region of the vertebral body exhibits lower density and more sparse microstructure. As compared to the anterior region, the posterior region shows higher density. These variations are more pronounced in vertebrae from older persons and in those adjacent to degenerated discs. Mixed results have been reported in regard to variation along the superior-inferior axis and to relationships between the heterogeneity in density and vertebral strength and fracture risk. These discrepancies highlight that, first, despite the large amount of study of the intra-vertebral heterogeneity in microstructure, direct study of that in mechanical properties has lagged, and second, more measurements of vertebral loading are needed to understand how the heterogeneity affects distributions of stress and strain in the vertebra. These future areas of study are relevant not only to the question of spine fractures but also to the design and selection of implants for spine fusion and disc replacement. The intra-vertebral heterogeneity in microstructure and mechanical properties may be a product of mechanical adaptation as well as a key determinant of the ability of the vertebral body to withstand a given type of loading.