Entheseal changes are traditionally included in a large array of skeletal features commonly referred to as “skeletal markers of activity.” However, medical studies and recent anthropological analyses of identified skeletal series suggest a complex combination of physiological and biomechanical factors underlying the variability of such “markers.” The aim of this study is to examine the relationship between age, sex, physical activity, and entheseal variability. To this end, 23 postcranial entheses are examined in a large (N = 484) Italian contemporary skeletal series using standardized scoring methods. The sample comprises subjects of known age, sex and, mostly, occupation. Results show a strong relationship between age and entheseal changes. Differences between sexes are also highlighted, while the effects of physical activity appear moderate. Altogether, our study indicates that entheseal morphology primarily reflects the age of an individual, while correlation with lifetime activity remains ambiguous. Am J Phys Anthropol 148:379–388, 2012. © 2012 Wiley Periodicals, Inc.