Light microscopy, particularly the use of polarized light, has such a high value for the differential diagnosis of dry bones that it can no longer be neglected. Alterations caused intra vitam by disease or other living conditions can clearly be differentiated by this technique from changes due to postmortem reactions (e.g., pseudopathology). As a reliable diagnosis is the basis not only of the study of case reports but also of the etiology and epidemiology of diseases in ancient populations, paleopathologists would be well-advised to employ histological analysis for their research, to avoid false diagnoses. The necessary basis for such research is the knowledge of the general histology, histogenesis, and growth as well as pathophysiology of bone. Some new techniques which facilitate the practical use of microscopic analysis, such as the preparation of thin-ground sections from undecalcified bone samples and nonrehydrated mummified soft tissues, are described. Selected examples of mechanisms of pathological bone changes, particularly the determination of vestiges of diseases in macerated bones by microscopy, are presented. Emphasis is placed on the differential diagnoses of proliferative reactions (e.g., periosteal processes of long bones and the skull). In this context, the importance of meningeal reactions on the endocranial lamina of the skull for morbidity and mortality in ancient populations is demonstrated. Furthermore, porotic hyperostosis of the skull vault and the orbital roof, i.e., the cribra cranii externa and cribra orbitalia, is discussed. Selected examples of the etiology and epidemiology of ancient diseases are presented (e.g., anemia, scurvy, rickets, and meningeal diseases), and ideas on living conditions and their implications for the origin and the spread of disease are given to establish a better understanding of deficiency and infectious diseases in the past. Yrbk Phys Anthropol 44:106–147, 2001. © 2001 Wiley-Liss, Inc.