Compartmentalization of the epithelial plasma membrane involves an apical (exposed to the lumen) and a basolateral (exposed to the extracellular matrix (ECM) and adjoining cells) domain, the identities of which are maintained by stereotypical organellar positioning and regulated intracellular trafficking of proteins and lipids. Since the 1970s, we have become aware of the capital importance of epithelial cell polarity for the functioning of organs, invasion by pathogens and development of cancer. However, the field seemed to lack a reliable system to study cell polarity. This rapidly changed owing to the pioneering work by Enrique Rodriguez-Boulan and David Sabatini, who established that virus-infected epithelial cells can serve as an excellent model to study molecular mechanisms of polarity establishment (Boulan & Sabatini, 1978).