Vascular smooth muscle cells (VSMCs) play intricate roles in both the physiological behavior and pathological alterations (e.g., the genesis of diseases such as atherosclerosis, vascular stiffening/calcification, aortic aneurysm and dissection) of blood vessels. By delving into the phenotypic responses of VSMCs to a range of mechanical cues, including hemodynamic forces, extracellular matrix stiffness, and topography, valuable insights can be gained into the mechanoreceptors and mechanotransduction pathways that enable these cells to sense and adapt to their physical environment. In addition to the existing research in this field, the authors' own expertise and experience are also incorporated. Their studies on mechanoreceptors (e.g., tyrosine kinase mechanoreceptors and nuclear mechanoreceptors) and the functional regulation of VSMCs are discussed, along with their investigation into the role of mechanoreceptors in the development and progression of vascular diseases such as arterial stiffening.