Approximately three fourths of middle-aged and older adults have at least two simultaneously occurring chronic conditions ("multiple morbidity," or MM), a trend expected to increase dramatically throughout the world. Rural residents, who tend to have fewer personal and health resources, are more likely to experience MM. To improve our understanding of the ways in which vulnerable, rural residents in the United States experience and manage MM, we interviewed 20 rural Appalachian residents with MM. We identified the following themes: (a) MM has multifaceted challenges and is viewed as more than the sum of its parts; (b) numerous challenges exist to optimal MM self-management, particularly in a rural, underresourced context; however, (c) participants described strategic methods of managing MM, including prioritizing certain conditions and management strategies and drawing heavily on assistance from informal and formal sources.