Although current therapies used in the treatment of HIV-1 infection have proven effective in reducing mortality due to the infection, the increase in drug resistant strains of the virus call for increased effort to explore and develop alternative treatment modalities. In this review, the various strategies to control HIV-1 replication through the disruption of Rev function are outlined. A wide range of methods have been developed including antisense DNA, ribozymes, decoy RNAs, transdominant proteins and suicide vectors targeted at disrupting Rev function. Although many of these methods have proven effective alone, it is hoped that a more robust antiviral response can be attained through combination of these strategies. As the methods of delivering these therapeutic agents matures through the development of lentiviral-based vectors, it is hoped that they will eventually reach the clinic where they may not only supplement the current treatment strategies but also provide resistance to those at high risk of infection or failing therapy.