Carbohydrate-binding proteins (CBP) can be isolated from a variety of species, including procaryotes (i.e. cyanobacteria), sea corals, algae, plants, invertebrates and vertebrates. A number of them, in particular those CBP that show specific recognition for mannose (Man) and N-acetylglucosamine (GlcNAc) are endowed with a remarkable anti-HIV activity in cell culture. The smallest CBP occur as monomeric peptides with a molecular weight of approximately 8.5 kDa. Many others are functionally dimers, trimers or tetramers, and their molecular weight can sometimes largely exceed 50 kDa. CBP can contain 2 to up to 12 carbohydrate-binding sites per single molecule, depending on the nature of the lectin and its oligomerization state. CBP qualify as potential anti-HIV microbicide drugs because they not only inhibit infection of cells by cell-free virus (in some cases in the lower nano- or even subnanomolar range) but they can also efficiently prevent virus transmission from virus-infected cells to uninfected T-lymphocytes. Their most likely mechanism of antiviral action is the interruption of virus entry (i.e. fusion) into its target cell. CBP presumably act by direct binding to the glycans that are abundantly present on the HIV-1 gp120 envelope. They may cross-link several glycans during virus/cell interaction and/or freeze the conformation of gp120 consequently preventing further interaction with the coreceptor. Several CBP were shown to have a high genetic barrier since multiple (>or=5) glycan deletions in the HIV envelope are necessary to provoke a moderate level of drug resistance. CBP are the prototypes of conceptionally novel chemotherapeutics with a unique mechanism of antiviral action, drug resistance profile and an intrinsic capacity to trigger a specific immune response against HIV strains after glycan deletions on their envelope occur in an attempt to escape CBP drug pressure.