Tat is a HIV-1 transaction transcriptional activator protein and plays a pivotal role in viral replication and in several AIDS-associated pathologies. Its biological properties and functions make it as a good candidate for the development of an anti-AIDS vaccine and/or drug. Strategies designing vaccines and drugs for anti-AIDS include vaccines derived from Tat, extracellular Tat-binding antagonists, inhibitors of Tat-activated intracellular second messengers, anti-Tat antisense, anti-TAR antisense, decoy and antagonists, anti-Tat intracellular intrabody, inhibitors of intracellular Tat cofactors and so on. An effective anti-AIDS therapy will require a multi-targeted approach in which classic antiviral drugs and protease inhibitors are combined with novel extracellular and intracellular Tat antagonists. This approach could prevent the development of drug-resistant HIV strains and decrease the dosage and related toxicity of each single drug and lead to a cure for AIDS-associated pathologies.