Understanding the mechanical function of bone material in relation to its structure is a fascinating but very complicated problem to resolve. Part of the complexity arises from the hierarchical structural organization of bone. Microhardness measurements, initially on relatively simply structured parallel-fibered bone, show a marked anisotropy in three orthogonal directions. This may, in part, be due to the highly anisotropic structure of the basic building block of bone, the mineralized collagen fibril. Microhardness measurements made face-on to the layers of crystals and collagen triple helical molecules, show much lower values than those made edge-on to these layers. Microhardness measurements of the much more complex “rotated-plywood” structure of lamellar bone, reveal the well-known general tendency toward anisotropy in relation to the long axis of the bone. A detailed examination of microhardness-microstructure relations of lamellar bone, however, shows that only in certain orientations can microhardness values be related directly to a specific attribute of the lamellar structure. Clearly, the gradual tilting and rotating of the mineralized collagen fibrils that form this structure produce a material that tends toward having isotropic microhardness properties, even though its basic building block is highly anisotropic. This may be an important structural attribute that allows lamellar bone to withstand a variety of mechanical challenges.