The Caliciviridae family includes human norovirus and sapovirus. These are a diverse set of viruses causing acute gastroenteritis (AGE) in people of all ages, with norovirus being responsible for approximately 20% of all AGE worldwide and sapovirus 3%–17% of AGE in children, respectively. Susceptibility to norovirus is associated with human genetics, with approximately one-fifth of the population being resistant to the predominant GII.4 genotype. A human enteroid model has recently been successfully established to address questions regarding pathogenesis and virus–host interactions. While no specific antivirals are available, norovirus vaccine candidates are in clinical trials.