Growing evidence indicates that critical steps in cancer progression such as cell adhesion, migration, and cell cycle progression are regulated by the composition and organization of the microenvironment. The adhesion of cancer cells to components of the microenvironment and the forces transmitted to the cells via the actinomyosin network and the signaling complexes organized within focal adhesions allow cancer cells to sense the local topography of the extracellular matrix and respond efficiently to proximal growth and migration promoting cues. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is over expressed in a variety of cancers and plays an important role in cell adhesion, migration, and anchorage-dependent growth. In this review, we summarize evidence which implicate FAK in the ability of cells to sense and respond to local forces from the microenvironment through the regulation of adhesion dynamics and actinomyosin contractility, and we discuss the potential roles of FAK as a mechanosensor in the progression of cancer.