People who inject drugs are more likely to be HIV positive and to have a mental disorder than the general population. We explore how the detection and treatment of mental illness among people who are injecting drugs are essential to primary and secondary prevention of HIV infection in this population. Aside from opioid addiction, few studies have been conducted on the links between mental disorders and injection-drug use. However, independent of the injection-drug use literature, a growing number of studies demonstrate that untreated mental illness, especially depression and alcohol/substance use disorders, is associated with HIV-related risk behaviors, acquiring HIV infection, failure to access HIV care and treatment, failure to adhere to HIV care and treatment, and increased morbidity and mortality from HIV-related diseases and comorbidities. In our review of both the published literature and gray literature we found a dearth of information on models for providing care for both opioid addiction and other mental illnesses regardless of HIV status, particularly in low- and middle-income countries. We therefore make recommendations on how to address the mental health needs of HIV-positive people who inject drugs, which include the provision of opioid substitution therapy and integrated mental health, substance abuse, and HIV services.