Non-enveloped viruses enclose their genome in capsids built of repetitive polypeptides interlinked with cementing proteins, divalent cations or disulphides. Interactions are broken in a stepwise manner during entry into cells leading to genome uncoating. Receptor or proteases induce conformational changes in case of rhinovirus, poliovirus or adenovirus, and thereby provide direct uncoating cues. Chemical cues from low endosomal pH activate rhinovirus or aphtovirus, and oxido-reductases mediate disulphide reshuffling of polyomavirus. Cellular motors provide a third class of cues as shown by adenoviruses. These examples highlight the diversity of cellular factors triggering virus uncoating, and offer new perspectives for the development of antivirals.