Insufficient concentrations and very short residence time of the anti-retroviral agents at the cellular and anatomical sites are among major factors that contribute to the failure of eradicating HIV from reservoirs and the development of multidrug resistance against antiretroviral agents. In recent years, nanotechnology-based drug delivery systems have shown remarkable ability to overcome many of the same anatomical and physiological barriers and deliver the therapeutic agents locally at the site of systemic diseases such as cancer.