It is the radiologist's cornerstone to decide if imaging findings are normal or abnormal and to differentiate between clinically significant and insignificant findings. This challenge is extremely common in routine clinical practice when performing magnetic resonance (MR) imaging of the spine because it is frequently performed to assess patients with cancer or with spine-related symptoms. MR appearance of the normal vertebral marrow shows important variations not only with age but also among individuals of the same age range. On the contrary, marrow distribution and signal intensity patterns show little variation among each vertebral body of the same subject. Focal alterations in signal intensity can be observed that reflect local variation in the amount of normal expected vertebral components, including fat and hematopoietic cells, bone, and vessels. A more recently recognized condition related to the presence of notochordal cells deserves further study because it could account for some frequent tiny marrow changes. Diffuse alteration in vertebral signal intensity can also be observed and can be difficult—or even impossible—to differentiate from diffuse marrow infiltration by an abnormal process, given the lack of specificity of MR imaging. This article highlights the normal variants and frequent alterations of the vertebral bone marrow as encountered on MR studies of the spine and that can simulate significant lesions.