Bioarcheology has made tremendous strides since the subdiscipline's inception, subsequent syntheses, the standardization of data collection methods, and analytical advances ranging from molecular analyses through age-estimation and biodistance. Concurrently, health and the adaptive success of past populations have remained primary concerns. However, questions are routinely raised about lesions and whether or not changing frequencies are synonymous with increases or decreases in stress, morbidity, and overall health. These include how and why healed lesions can simultaneously represent stress and survival, demanding that researchers understand how population dynamics influence skeletal sample formation. In this study, methods to analyze age- and sex-specific mortality patterns prior to, and in conjunction with, the analysis of linear enamel hypoplasias are demonstrated. Paleodemographic and paleoepidemiological models are presented for late Pre-Columbian skeletal samples from the Eastern Woodlands. Results of hazard modeling demonstrate that elevated mortality rates were commonplace during the latter half of the Mississippian period (AD 1200–1450) with reproductive-age females experiencing high age-specific risk of death attributed to the development of fortified villages and novel environments for increased pathogen loads. Corollary results are presented for the age-specificity of linear enamel hypoplasias in the central Illinois River valley. The epidemiological models demonstrate that the relationship between adult mortality and early childhood stress varied through space, culture, and time. These findings highlight the need to effectively operationalize measurements related to health and stress in past populations and support the adoption of selective mortality and heterogeneity in frailty as key concepts in bioarcheological research. Am J Phys Anthropol 155:268–280, 2014. © 2014 Wiley Periodicals, Inc.