Both human immunodeficiency virus (HIV) and illicit drug addiction remain major health problems not only in the United States but all over globe. The effect of drug addiction on HIV/AIDS (acquired immunodeficiency syndrome) has been somewhat underexplored. However, in United States more than one fourth of HIV-positive individuals are injection drug users. Opiates are known to negatively affect the immune system, and therefore may have deleterious effects on progression of disease among HIV-infected individuals. This review discusses the effects of opiates on immune system as well as its effect on HIV replication and AIDS progression. In addition, the effects of opiates on disease progression in non-human primate model of AIDS is presented with at least one possible reason for rapid disease progression in multi-virus the challenge model.