The primary cilium is an antenna-like projection from the plasma membrane that serves as a sensor of the extracellular environment and a crucial signaling hub. Primary cilia are generated in most mammalian cells, and their physiological significance is highlighted by the large number of severe developmental disorders or ciliopathies that occur when primary ciliogenesis is impaired. Primary ciliogenesis is a tightly regulated process, and a central early regulatory step is the removal of a key mother centriole capping protein, CP110 (also known as CCP110). This uncapping allows vesicles docked on the distal appendages of the mother centriole to fuse to form a ciliary vesicle, which is bent into a ciliary sheath as the microtubule-based axoneme grows and extends from the mother centriole. When the mother centriole migrates toward the plasma membrane, the ciliary sheath fuses with the plasma membrane to form the primary cilium. In this Review, we outline key early steps of primary ciliogenesis, focusing on several novel mechanisms for removal of CP110. We also highlight examples of ciliopathies caused by genetic variants that encode key proteins involved in the early steps of ciliogenesis.