A growing literature on deaths of despair has argued that workers’ declining life expectancy in deindustrialized rustbelt areas in the U.S. and the associated deepening of health inequalities signal the profound existential crisis of contemporary capitalism. Competing explanations downplay the negative consequences of “creative destruction” and focus instead on unhealthy lifestyles. This article contributes to this debate by presenting the first empirical analysis of the role of deindustrialization in the deaths of despair epidemic that hit Eastern Europe in the 1990s. Drawing on the thematic analysis of 82 semi-structured interviews in four deindustrialized towns in Hungary, the article constructs a general sociological framework for analyzing deaths of despair applicable to other rustbelt areas. Deindustrialization engenders individual and social processes that affect health by increasing stress and eroding coping resources. By conceptualizing deindustrialization as a fundamental cause of ill health, sociology has great potential to contribute to understanding the root causes of deaths of despair.