The treatment of injection drug users (IDUs) coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) presents multiple challenges, many of which could be addressed by the development of directly observed therapy programs. This is made all the more feasible by the validation of once-daily treatment regimens for HIV. We have demonstrated that virological suppression can be achieved and maintained in as many as 80% of active IDUs who have received highly active antiretroviral therapy for 48 months. This approach has now been validated in first- and second-line therapy, as well as for the treatment of bacterial infections in this population, achieving therapeutic results similar to those reported in the general population. The model is now being applied to the treatment of HCV infection, focusing on patients with infection due to HCV genotype 2 or 3, in whom the likelihood of response may exceed 80%. Our ultimate goal is to ensure that, even in treating IDUs in the inner city, no patient is left behind.