This commentary explores the relationships between homelessness, drug use and hepatitis C infection, within the broader context of social exclusion. Although it is difficult to estimate the number of homeless people who are misusing drugs or the number of drug users who are homeless, UK and international literature indicate a significant overlap between the two groups. Homeless drug users (HDUs) tend to experience many life problems and their situation has been described as a double jeopardy [Neale, J. (2001). Homelessness amongst drug users: A double jeopardy explored. The International Journal of Drug Policy, 12, 353-369]. Compounding this, emerging data now show that HDUs are at increased risk of being infected with the hepatitis C virus (HCV). The concept of social exclusion is critically reviewed as a means of understanding the experiences and needs of HDUs infected with HCV and, in light of this, policy and practice are discussed. It is argued that efforts to tackle broader social problems are indirectly assisting this vulnerable group, but more joined-up strategies and targeted measures are still required. These include tackling negative community and professional attitudes and discriminatory practices; more integrated service provision and professional training; and drawing HDUs with HCV into policy and practice debates as advisors, educators and collaborators. To conclude, suggestions for future research that would help to clarify some of the complexity surrounding the behaviours, experiences and service needs of HDUs with HCV are made.