Norovirus (NoV), a member of the family Caliciviridae, is a major cause of acute water- and food-borne nonbacterial gastroenteritis and forms antigenically diverse groups of viruses. Human NoVs are divided into at least three genogroups, genogroups I (GI), GII, and GIV, which contain at least 15, 18, and 1 genotypes, respectively. Except for a few genotypes, all NoVs bind to histo-blood group antigens (HBGAs), namely ABH antigens and Lewis antigens, in which carbohydrate core structures, (types 1 and 2) constitute antigenically distinct phenotypes. Volunteer challenge studies have indicated that carbohydrate binding is essential for genogroup I genotype 1 (GI/1) infection. Non-secretors who do not express FUT2 fucosyltransferase, and consequently do not express H type 1 or Lewis b antigens in the gut, are not infected after challenge with GI/1. NoV virus-like particles (VLPs), which are recombinant particles that are morphologically and antigenically similar to the native virion, display different ABH and Le carbohydrate-binding profiles in vitro. Epidemiological studies have shown that individuals with different ABH phenotypes are infected with NoV strains in a genotype-specific manner. On the other hand, an in vitro binding assay using NoV VLPs showed a uniform recognition pattern against type 1 and 2 core structures, and bind more tightly to type 1 carbohydrates than to type 2. Type 1 carbohydrates are expressed at the surface of the small intestine and are presumably targeted by NoV. This property may afford NoV tissue specificity. GII/4 includes global epidemic strains and binds to more HBGAs than other genogroups. This characteristic may be linked to the worldwide transmission of GII/4 strains. Although it is still unclear whether HBGAs act as primary receptors or enhance NoV infectivity, they are important factors in determining tissue specificity and the risk of transmission.