The advent of combination antiretroviral therapy (cART) has transformed HIV-1 infection into a controllable chronic disease, but these therapies are incapable of eradicating the virus to bring about an HIV cure. Multiple strategies have been proposed and investigated to eradicate latent viral reservoirs from various biological sanctuaries. However, due to the complexity of HIV infection and latency maintenance, a single drug is unlikely to eliminate all HIV reservoirs and novel strategies may be needed to achieve better efficacy while limiting systemic toxicity. In this review, we describe HIV latency in cellular and anatomical reservoirs, and present an overview of current strategies for HIV cure with a focus on their challenges for clinical translation. Then we provide a summary of nanotechnology solutions that have been used to address challenges in HIV cure by delivering physicochemically diverse agents for combination therapy or targeting HIV reservoir sites. We also review nanocarrier-based gene delivery and immunotherapy used in cancer treatment but may have potential applications in HIV cure.