Human norovirus (hNoV) infections cause acute gastroenteritis, accounting for millions of disease cases and more than 200,000 deaths annually. However, the lack of in vitro infection models and robust small-animal models has posed barriers to the development of virus-specific therapies and preventive vaccines. Promising recent progress in the development of a norovirus infection model is reviewed in this article, as well as attempts and efforts made since the discovery of hNoV more than 40 years ago. Because suitable experimental animal models for human norovirus are lacking, attractive alternatives are also discussed.