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In epithelial cells, the polarized orientation of the apical–basal axis determines the position of the apical lumen and, thereby, the collective tubular tissue architecture. From recent studies employing 3D cell cultures, animal models, and patient material, a model is emerging in which the orientation and positioning of the apical surface and lumen is controlled by the relationships between the extracellular matrix (ECM), Rho family GTPase signaling, recycling endosome dynamics, and cell division. Different epithelial cells adjust these relationships to establish their specific cell polarity orientation and lumen positioning, according to physiologic need. We provide an overview of the molecular mechanisms required to construct and orient the apical lumen.