Mechanotransduction by vascular smooth muscle (VSM) is defined as a cellular response (contraction, secretion, growth, division) to transmural pressure or stretch. This review includes an overview of the physical forces VSM cells experience in vivo, consideration of experimental techniques used to study VSM mechanotransduction, and a discussion of the scientific literature pertinent to the individual cellular components that have been implicated in the transduction of physical forces. These include: the extracellular matrix, integrins, ion channels, the sarcoplasmic reticulum, second messenger systems, contractile proteins, and the cytoskeleton.