As the HIV pandemic rapidly spread worldwide in the 1980s and 1990s, a new approach to treat cancer, genetic diseases, and infectious diseases was also emerging. Cell and gene therapy strategies are connected with human pathologies at a fundamental level, by delivering DNA and RNA molecules that could correct and/or ameliorate the underlying genetic factors of any illness. The history of HIV gene therapy is especially intriguing, in that the virus that was targeted was soon co-opted to become part of the targeting strategy. Today, HIV-based lentiviral vectors, along with many other gene delivery strategies, have been used to evaluate HIV cure approaches in cell culture, small and large animal models, and in patients. Here, we trace HIV cell and gene therapy from the earliest clinical trials, using genetically unmodified cell products from the patient or from matched donors, through current state-of-the-art strategies. These include engineering HIV-specific immunity in T-cells, gene editing approaches to render all blood cells in the body HIV-resistant, and most importantly, combination therapies that draw from both of these respective "offensive" and "defensive" approaches. It is widely agreed upon that combinatorial approaches are the most promising route to functional cure/remission of HIV infection. This chapter outlines cell and gene therapy strategies that are poised to play an essential role in eradicating HIV-infected cells in vivo.