This chapter reviews the different antiviral approaches with dendrimers with a particular focus on the strategy based on multivalent non-covalent human immunodeficiency virus (HIV) entry inhibitors. It describes the poly(phosphorhydrazone) dendrimers were used as building blocks for the preparation of multivalent analogs of GalCer. The chapter discusses the strategy that proposes to use the affinity of the virus for GalCer to inhibit HIV entry into cells. Gene expression of HIV-1 could be inhibited by molecules targeting viral gene regulatory proteins that drastically enhances the efficiency of viral transcription, such as Tat or its molecular targets. The Tat-TAR interactions are crucial to ensure an efficient viral transcription. The recognition of DC-SIGN involves multivalent interaction with mannose-rich glycoproteins of pathogens; dendrimers and other multivalent scaffolds have been successfully used to target these interactions. The design of multivalent inhibitors or ligands targeting cell receptors is directly inspired by the existence of polyvalent interactions in biological systems.