Social marginalization is associated with poor health outcomes for affected people. However, in a psychosocial study of treatment for hepatitis C infection conducted in Sydney, Australia, participants living in socially disadvantaged circumstances applied adaptive approaches learned from past experiences of drug dependence, living with symptoms of chronic illness, coping with depression and childhood sexual abuse to enable them to cope with severe treatment-related side-effects. This finding has implications for the clinical management of hepatitis C treatment; the factors and processes that facilitate adaptive coping to adversity associated with social marginalization can be assessed for their clinical contribution to coping with an arduous regimen.