Stigma poses significant challenges to those with chronic hepatitis C (CHC), their social networks, communities, and society. This study's purpose was to identify and describe how people lived with CHC and made self-care decisions. Data are presented from interviews and daily recordings of 26 study participants. Experiences of stigma were attributed primarily to misconceptions about the cause and transmission of the disease and its association with illicit drug use. Perceptions and responses to stigma were context-dependent, flexible, and varied over time. Stigma created barriers to access of health services and undermined the social supports required to address self-care needs and illness management. The extent and severity of stigma suggests that interventions to reduce or eliminate stigma will require individual, structural, and systemic changes. Further study is required to clarify the relationship between the trajectory of CHC and the experience and responses to stigma.