Human environments in the Modern period are characterized by a complex set of political, economic, social, cultural, ecological, and biocultural interactions. This chapter uses historical and bioarchaeological evidence to understand the human experience of pellagra at the intersection of these forces in the 19th and 20th century in the Veneto region of Italy. As new foods were imported from across the Atlantic, socio-political and economic forces conspired to make a growing class of people particularly vulnerable to micronutrient deficiency and disease. In the context of Enlightenment and positivist values, medicalization and institutionalization were also a growing force for understanding and coping with strange, inconvenient, or disturbing differences in human health and behavior. These combined forces shaped the reality for sufferers of pellagrous mania. This chapter considers the human skeletal material from pellagra sufferers confined to Sant’Anna Ospedale in the century between 1850 and 1950 and situates them in the context of asylum records from two nearby manicomio to trace the embodiment of disease ideology and treatment in the context of a changing social environment. These data have implications for understanding how environmental change opens a space for changing disease landscapes, which, in cases of highly disfiguring conditions or deeply disturbing behavioral changes, creates an opening for deepening marginalization, social division, and social control.