These last years, numerous molecules have been developed to face HIV-1 infection. All viral replication steps are potential targets for new molecules. The most potent inhibitors of virus-cell adsorption are represented by the different sulfated, sulfonated and carboxylated polymers among which aurintricarboxylic acid (ATA). The soluble CD4 are also potent inhibitors of viral adsorption in vitro. Many compounds are active at the level of the reverse transcriptase (RT), particularly the 2',3'-dideoxynucleosides, represented by the three currently most used drugs in the clinic, AZT, ddC and ddI. The acyclic nucleoside phosphonates (PMEA, PMEDAP) have shown a broad spectrum activity against many human and animal retroviruses, and also unique pharmacological properties allowing infrequent administration. Finally, most recently, highly potent activity, without toxicity, has been demonstrated by TIBO, HEPT and other HIV-1 RT-specific inhibitors.