This collection reviews our understanding of the molecular mechanisms involved in establishing and maintaining cell polarity, as well as their relevance for human disorders. Contributors discuss how cells coordinate signaling pathways, membrane trafficking, and cytoskeletal remodeling to ensure proper spatial arrangement of cellular components. Processes such as transcytosis, exocyst-mediated vesicle trafficking, and endosomal sorting are covered in detail. Throughout, the focus is on epithelial cells and how polarity mechanisms facilitate the development of their apical and basolateral surfaces, tube formation, exchange of waste and nutrients, and the generation and maintenance of specialized structures at the cell surface.