Gene therapeutic strategies for the treatment of human immunodeficiency virus type 1 (HIV-1) infection have received increased attention due to lack of chemotherapeutic drugs or vaccines that show long-term efficacy in vivo. An emerging group, referred to here as "genetic antivirals," is reviewed. Genetic antivirals are defined as DNA or RNA elements that are transferred into cells and affect their intracellular targets either directly, or after expression as RNA or proteins. They include antisense oligonucleotides, ribozymes, RNA decoys, transdominant mutants, toxins, and immunogens. They offer the possibility to target simultaneously multiple sites in the HIV genome, thereby minimizing the production of resistant viruses. We review the molecular mechanisms of genetic antivirals, their HIV molecular targets, and discuss issues concerning their application as anti-HIV agents.