Over the past decade, the Hippo tumor suppressor pathway has emerged as a central regulator of growth in epithelial tissues. Research in Drosophila and in mammals has shown that this kinase signaling cascade regulates the activity of the transcriptional coactivator and oncoprotein Yorkie/Yap. In this review, we discuss recent findings that emphasize the cell cortex—specifically the actin cytoskeleton, intercellular junctions, and protein complexes that determine cell polarity—as a key site for Hippo pathway regulation.