Antiretroviral therapy with potent combinations of drugs has been responsible for a significant decline in the occurrences of AIDS defining conditions and death in the developed world. However, therapy requires lifelong use and is complicated by relatively high failure rates, significant toxicities, adherence difficulties and the development of resistance. The combination of these complications of therapy and the availability of this treatment to only 1 in 20 of the estimated 34 million people infected world wide has prompted us to reconsider the current strategies for achieving the goals of HIV therapy. A more rational approach to therapeutic interactions is needed, particularly with respect to therapy in the developing world, with the focus shifted towards maintaining relative viral control over the long term. One potential mechanism to attain viral control over the long term is the use of therapeutic vaccines. This chapter will review the scientific rationale for therapeutic HIV-1 vaccines and the vaccines that have been evaluated as a therapeutic to date including recombinant envelope glycoproteins, inactivated envelope depletd virus, regulatory proteins such as Tat, cytokines such as IFN-α, DNA vaccines, and live viral vectors. Although the future role of therapeutic vaccines in the treatment of HIV-1 remains to be determined, at a minimum this immunomodulatory approach will provide new insights into fundamental viral-host cell interactions and the pathogenesis of HIV-1. Yet even more notable, is that, if successful, a therapeutic vaccine product would be inexpensive and rapidly exportable representing a treatment strategy for people living with HIV infection worldwide.