Cells have a mechanism that converts physical forces into biochemical signals, a critical process known as “mechanotransduction.” Mechanotransduction plays a vital role in regulating multiple developmental and homeostatic events, including skeletal formation. Although underappreciated for decades, accumulated evidence now suggests that primary cilia play an important role in transducing mechanical stimuli. Since defects in the cilia result in multiple skeletal diseases, the importance of understanding the mechanisms between the mechanotransductive role of the cilia and skeletal health is paramount. However, the cellular mechanism of how cilia function as mechanosensors to control skeletal growth and homeostasis remains unclear. In addition, little is known about whether the manipulation of ciliary signaling related to defective mechanotransduction improves the skeletal disease conditions seen in osteoarthritis and osteoporosis. In this chapter, we provide a comprehensive overview of cilia and their role in mechanotransduction during skeletal development, with a focus on the function of key ciliary genes and intracellular signaling pathways in different skeletal cell types. We also highlight the broad impact of ciliary defects on mechanical stress-related skeletal diseases.