Human noroviruses interact with both human histo-blood group antigens (HBGAs) and human milk oligosaccharides (HMOs). The former is believed to be important for a virus infection, while the latter might act as a natural decoy in the host during an infection. However, certain noroviruses are known to bind poorly to HBGAs, yet still cause infections; some interact with numerous HBGA types, but are non-prevalent; and yet others bind HBGAs and seem to be increasing in prevalence. HBGAs and HMOs can be found as soluble antigens in humans, both can be structurally alike, and both can interact with equivalent residues at an identical binding pocket on the capsid. In this Gem, we discuss HBGA and HMO binding studies for human noroviruses, concentrating on the clinically important genogroup II noroviruses. In short, the roles of HBGA and HMO interactions are still an unclear in a norovirus infection.