The term multivalency (polyvalency) in the biological science is defined as the simultaneous binding of multiple ligands to one receptor (or multiple receptors to one ligand). The possibility of gaining potency and selectivity was significantly increased through the use of multivalent ligand as a homo- or hetero-dimer, thus multivalent ligands provided a more attractive strategy to design novel anti-HIV agents with therapeutic applications. Moreover, similar to phenomenon of multivalency, an alternative strategy is called the "mixed sites inhibitor", viz. a single molecule that possesses enough chemical space to maximize interactions with its complementary binding pocket, or to bind simultaneously in more than one regions in a target. Actually, the addition of a third heterocyclic nucleus to the parent compound resulted in "mixed sites" anti-HIV agents with broad spectrum of activities against the mutant HIV-1 strains. Based on current representative examples, the present article provided a brief review on the rationale for the design of different classes of multivalency anti-HIV agents and also discussed the advantages over their monomeric counterparts, providing a novel paradigm to facilitate the development of anti-HIV/AIDS therapeutic agents in treatment of HIV infected community.