Disrupted cell polarity is a feature of epithelial cancers. The Crumbs, Par and Scribble polarity complexes function to specify and maintain apical and basolateral membrane domains, which are essential to organize intracellular signaling pathways that maintain epithelial homeostasis. Disruption of apical-basal polarity proteins facilitates rewiring of oncogene and tumor suppressor signaling pathways to deregulate proliferation, apoptosis, invasion and metastasis. Moreover, apical-basal polarity integrates intracellular signaling with the microenvironment by regulating metabolic signaling, extracellular matrix remodeling and tissue level organization. In this review, we discuss recent advances in our understanding of how polarity proteins regulate diverse signaling pathways throughout cancer progression from initiation to metastasis.