The cytoplasmic side of focal adhesions is comprised of large molecular complexes that link transmembrane receptors, such as integrins, to the actin cytoskeleton and mediate signals modulating cell attachment, migration, proliferation, differentiation, and gene expression. These complexes are heterogeneous and dynamic structures that are apparent targets of regulatory signals that control the function of focal adhesions. Recent studies using genetic approaches in invertebrate and vertebrate systems have begun to reveal the structure and function of these complexes in vivo.