Drugs of abuse, such as opiates, have been widely associated with enhancing susceptibility to HIV infection, intensifying HIV replication, accelerating disease progression, diminishing host-immune responses, and expediting neuropathogenesis. In this talk, I will present a variety of mathematical models to study the effects of the drugs of abuse on several aspects of HIV infection and replication dynamics. The models are parameterized using data collected from simian immunodeficiency virus infection in morphine-addicted macaques. I will demonstrate how mathematical modeling can help answer critical questions related to the HIV infection altered due to the presence of drugs of abuse. Our models, related theories, and simulation results provide new insights into the HIV dynamics under drugs of abuse. These results help develop strategies to prevent and control HIV infections in drug abusers.