The provision of care and support to persons living with human immunodeficiency virus (HIV) in Brazil who also use drugs and/or alcohol represents special challenges because of the combined effects of addiction, poverty, stigma, and discrimination. This paper presents details on a program providing both clinic- and field-based care to HIV-infected injection drug users, highlighting the use of a specialized case management approach to address the clinical and psychosocial needs of this population. This program includes both a mobile case management team that fosters group discussions and provides individual counseling, and provision of medical consultations at 2 major drug treatment centers in Rio de Janeiro. The article also describes the experience of working with injection drug users who regularly attend an outpatient clinic serving marginalized communities through the use of mutual self-help groups and specialized support groups to address to issue of adherence to antiretroviral therapies for the treatment of HIV/acquired immunodeficiency syndrome.