Dental enamel hypoplasias are deficiencies in enamel thickness resulting from physiological perturbations (stress) during the secretory phase of amelogenesis. The results of a wide variety of experimental, clinical, and epidemiological studies strongly suggest that these defects and their associated histological abnormalities (such as accentuated stria of Retzius and Wilson bands) are relatively sensitive and nonspecific indicators of stress. Because of the inability of enamel to remodel, and the regular and ring-like nature of their development, these defects can provide an indelible, chronological record of stress during tooth crown formation. For these reasons, along with the ease with which they are studied, enamel hypoplasias have been increasingly employed as indicators of nutritional and disease status in paleopathology, and their study has begun to extend into other subdisciplines of physical anthropology. In order to provide the reader with a better understanding of the current issues in this field, we first review normal enamel development, historical advances in the study of enamel developmental abnormalities, and provide a threshold model to help conceptualize the etiology of enamel developmental defects. Specific attention is then centered on extant, fundamental issues in the use of enamel hypoplasias and histological structures as epidemiological indicators of nonspecific stress. Most enamel hypoplasias are associated with abnormal histological changes (accentuated stria of Retzius or “Wilson” and “Cluster” bands). However, the lack of association of some mild surface irregularities, characteristically seen as thin, perikymata-like surface depressions, with abnormal prism morphology suggests that these surface features may not be evidence of physiological perturbation. Methods now exist to reliably identify both histological and enamel surface defects. However, further research is needed on methods for determining the size of defects and the epidemiological significance of defect widths and depths. Similarly, the general relationship between the location of enamel hypoplasias and associated histological structures on the one hand, and an individual's age at the time of their development on the other hand, is also well understood. However, better estimates of intra- and inter-population variation in the timing of enamel matrix formation are needed before these defects can reach their full potential as chronometric measures of stresses. Lack of understanding patterns of differential susceptibility of enamekl to developmental disruption has likely hindered interpretations of the results of a number of past experiments. The seemingly strong pattern of differential suscetibility of enamel to disruption-within teeth and across tooth classes, dentitions, and taxa-may yield a number of significant clues to understanding basic issues in enamel development. Populations that are exposed to a high degree of undernutrition and disease, from prehistoric to contemporary times, share high rates of linear enamel hypoplasias. While these defects seem to relate to bouts of undernutrition and infection, their specific etiology is still unknown. In the next decade we expect to develop more precise information on the specificity and sensitivity of secretory ameloblaste to disruption. A variety of research directions are suggested for further anthropological study.