Within many mechanosensitive tissues and organs such as vascular endothelium, renal and liver epithelium, and bone, the cells residing within them are exposed to fluid flow. The process by which flow-induced mechanical loads are sensed by these cells and transduced into a biochemical signal is mostly unknown. The primary cilium is a rod-like, microtubule-based structure that projects from the cell surface into the extracellular environment. By possessing (1) mechanical characteristics that allow it to deflect under fluid flow, and (2) a number of receptors, channels, and signaling molecules, the primary cilium is uniquely suited to function as a cellular “flow sensor”. In our review of the primary cilium and its role in sensing of fluid flow, we consider ciliary mechanobiology from both biological and mechanical perspectives. The first part of this chapter focuses on comparing and contrasting ciliary flow sensing mechanisms in kidney epithelial cells, cardiovascular endothelial cells, bile duct epithelial cells, nodal cells, and bone cells. We demonstrate that ciliary sensation of fluid flow can involve molecular mechanisms that are shared across diverse cell types, yet can also uniquely differ between cell types as well. The second part of this chapter focuses on ciliary mechanics. In particular, we review the contribution of various ciliary components to the mechanical behavior of the cilium, and efforts to mechanically model cilium deflection under flow.