Primary cilia project from the surface of most vertebrate cells, and function in sensation and signaling during both development and adult tissue homeostasis. Mounting evidence links ciliary defects with a wide variety of diseases, underscoring the importance of understanding how these dynamic organelles are assembled and maintained. However, despite their physiological and clinical relevance, the logic and machinery that regulate ciliogenesis remain largely enigmatic. Here, we summarize emerging data that connect the assembly and disassembly of the primary cilium to cell cycle progression and we examine how determinants of cell architecture, including the planar cell polarity pathway, may regulate ciliogenesis. Additionally, identification of the genes underlying diverse ciliopathies in human patients is shedding light on the regulation of the formation of this complex organelle. Developmental Dynamics 237:1972–1981, 2008. © 2008 Wiley-Liss, Inc.